USP37 Data Analysis

HGNC Gene Name: ubiquitin specific peptidase 37
HGNC Gene Symbol: USP37
Identifiers: hgnc:20063 NCBIGene:57695 uniprot:Q86T82
Orthologs: mgi:2442483 rgd:2319715
INDRA Statements: deubiquitinations all statements
Pathway Commons: Search for USP37
Number of Papers: 50 retrieved on 2023-02-19

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol	Name	DepMap Correlation
TIPIN	TIMELESS interacting protein	0.248
THAP11	THAP domain containing 11	-0.207
RAD17	RAD17 checkpoint clamp loader component	0.205
LETM1	leucine zipper and EF-hand containing transmembrane protein 1	-0.204
ORC4	origin recognition complex subunit 4	0.204
UTP4	UTP4 small subunit processome component	-0.203
APEX2	apurinic/apyrimidinic endodeoxyribonuclease 2	0.201

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP37using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier	GO Name	GO Type	p-value	p-value (adj.)	q-value
GO:0000076	DNA replication checkpoint	Biological Process	1.40e-05	1.56e-03	5.44e-04
GO:0008156	negative regulation of DNA replication	Biological Process	9.04e-05	1.01e-02	1.27e-03
GO:0006260	DNA replication	Biological Process	9.77e-05	1.09e-02	1.27e-03

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP37 using CRISPR-Cas9.

Knockout Differential Expression

Symbol	Name	log₂-fold-change	p-value	p-value (adj.)
MMP1	matrix metallopeptidase 1	4.51e-01	1.38e-08	1.53e-04
PTMA	prothymosin alpha	-3.32e-01	1.01e-08	1.53e-04

Gene Set Enrichment Analysis

There were too few differentially expressed genes to run a meaningful GSEA.

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP37 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

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USP37 deubiquitinates MYC. 8 / 8

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Lastly, USP37 deubiquitinates and stabilizes the proto-oncogene c-Myc and the oncogenic fusion PLZF-RARA, suggesting that inhibition of USP37 DUB activity could have therapeutic potential XREF_BIBR, XREF_BIBR.

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Recent evidence has revealed that c-Myc can be deubiquitylated and regulated by USP28, USP36 and USP37.

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USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer.

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Further studies indicate that USP37 directly interacts with c-Myc and deubiquitinates c-Myc in a DUB activity dependent manner.

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An early study showed that USP28 deubiquitinates c-Myc via interacting with Fbw7alpha whereas a recent study reveals that USP37 deubiquitinates c-Myc independently of Fbw7 and c-Myc phosphorylation.

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USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer.

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Further studies indicate that USP37 directly interacts with c-Myc and deubiquitinates c-Myc in a DUB activity-dependent manner.

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USP37 deubiquitinates CDT1. 7 / 7

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USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

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USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

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USP37 regulates DNA replication by deubiquitinating CDT1, an important protein in DNA replication, but USP37 may control many unknown factors at replication forks that should be further explored [48].

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USP37 induces deubiquitination of CDT1, whereas a catalytically inactive (C350S) USP37 mutant is unable to ubiquitinate CDT1, further suggesting that USP37 plays a role in CDT1 stabilization.

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USP37 interacted with and deubiquitinated CDT1 to protect it from proteasomal degradation.

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USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 invivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin.

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The role of cysteine 350 in USP37 was first illustrated by Huang et al. in 2011, in which they found that CDK2 activates USP37 to antagonize APC (CDH1) and promote S phase entry and that USP37 deubiquitinates CDT1 [19].

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USP37 deubiquitinates Cyclin. 4 / 4

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USP37 deubiquitinates and stabilizes Cyclin A and promotes S phase entry.

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Usp37 binds APC/C Cdh1 in G1 and deubiquitinates the APC/C substrate cyclin A [XREF_BIBR].

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Deubiquitination and stabilization of the APC/C substrate cyclin A by USP37 enables entry into S phase.

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These results argue that USP37 deubiquitinates cyclin A directly as opposed to being an EMI1-type APC/C inhibitor.

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USP37 deubiquitinates WAPL. 3 / 3

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Next, to investigate whether USP37 can directly deubiquitylate WAPL, we purified full-length USP37 WT and USP37 C350A from Sf9 insect cells and added either USP37 WT, USP37 C350A, or buffer alone to a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Importantly, when USP37 WT, but not USP37 C350A, is added, ubiquitylation is reduced, indicating that USP37 can directly deubiquitylate WAPL and/or WAPL associated proteins in vitro.

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WAPL is pulled down with His Ub under denaturing conditions in all tested treatments, indicating that ubiquitylated WAPL is detected throughout the cell cycle.We expected that, if USP37 deubiquitylate[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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USP37 deubiquitinates SNAI1. 3 / 3

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Our studies demonstrate that a deubiquitinating enzyme (DUB) family member, USP37, can deubiquitinate Snail and prevent degradation of Snail.

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Microarray analysis of total RNA isolated from stable PLAGL2 knockdown (SGC7901-shRNA) and SGC7901 NC cells elucidated three differentially expressed DUBs, of which only USP37 directly interacted and significantly diminished the ubiquitination of SNAI1.

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Subsequent sub-screening identified 23 DUBs that interact with SNAI1, out of which USP29, USP36, and USP37 upregulate and reduce polyubiquitination of the SNAI1 protein.

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USP37 leads to the deubiquitination of CDKN1B. 2 / 2

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Constitutive expression of USP37 promotes p27 deubiquitination in medulloblastoma cells, whereas a catalytically dead USP37 mutant is unable to stabilize p27.Dobson et al. further explored the molecular basis of REST-induced USP37 downregulation and found that USP37 supresses medulloblastoma tumor growth in an orthotopic mouse model by modulating its downstream targets [87].

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Ectopically expressed wild-type USP37 formed a complex with p27, promoted its deubiquitination and stabilization and blocked cell proliferation.

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USP37 deubiquitinates BLM. 2 / 2

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Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response.

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Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR).

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USP37 deubiquitinates IFI27. 1 / 1

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Ectopically expressed wild-type USP37 formed a complex with p27, promoted its deubiquitination and stabilization and blocked cell proliferation.

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USP37 deubiquitinates CCNA2. 1 / 1

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Flow cytometry analysis of the HBx-expressing cells showed deregulation of cell cycle apparently due to the enhanced gene expression and stabilization of USP37 protein and deubiquitination of Cyclin A by USP37.

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USP37 leads to the deubiquitination of EPAS1. 1 / 1

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USP37 promotes deubiquitination of HIF2alpha in kidney cancer.

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USP37 deubiquitinates H2AC17. 1 / 1

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USP37 deubiquitinates CCNA1. 1 / 1

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USP37 deubiquitinates Cyclin on G1. 1 / 1

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For example, USP37 deubiquitinates cyclin A during G1 phase causing cyclin A stabilization and timely entry into S phase 14.

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USP37 deubiquitinates ZBTB16. 1 / 1

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The deubiquitinating enzyme USP37 regulates the oncogenic fusion protein PLZF/RARA stability.

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USP37 deubiquitinates Cyclin on T293. 1 / 1

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We investigated deubiquitination of cyclin A by USP37 in 293T cells cotransfected with Myc-cyclin A, HA-ubiquitin, and either USP37 or USP37DD.

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Modified USP37 leads to the deubiquitination of CDKN1B. 1 / 1

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Constitutive USP37 expression promotes p27 deubiquitination.

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USP37 leads to the deubiquitination of CCP110. 1 / 1

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In addition, over-expression of two unrelated DUBs, USP1 and USP37, did not promote CP110 de-ubiquitylation (XREF_FIG and data not shown).

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USP37 deubiquitinates CHEK1. 1 / 1

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We further demonstrated that USP37 deubiquitinates CHK1, promoting its stability.

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USP37 deubiquitinates FBXW7. 1 / 1

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An early study showed that USP28 deubiquitinates c-Myc via interacting with Fbw7alpha whereas a recent study reveals that USP37 deubiquitinates c-Myc independently of Fbw7 and c-Myc phosphorylation.

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Modified USP37 leads to the deubiquitination of GLI1. 1 / 1

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Moreover, overexpression of USP37 in breast cancer promoted stemness, cell invasion, and chemoresistance by deubiquitinating the glioma associated oncogene 1 protein XREF_BIBR.

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Ubiquitinated USP37 leads to the deubiquitination of USP37. 1 / 1

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The level of USP37 ubiquitination was also reduced by mutations in UIM2 or UIM3, suggesting their role in ubiquitination of USP37 itself.

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Other Statements

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USP37 affects cell population proliferation

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USP37 inhibits cell population proliferation.

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USP37 inhibits cell population proliferation. 5 / 7

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These findings indicate that ectopic USP37 not only blocked REST dependent cell proliferation, but also countered the blockade to neuronal differentiation even in the presence of REST.

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Since concomitant loss of REST and USP37 expression attenuated p27 stabilization and differentiation and rescued cell proliferation, our data strongly suggest that repression of USP37 and consequent p27 degradation, are important for REST dependent maintenance of cell proliferation.

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Functionally , downregulated USP37 decreases cell proliferation and anchorage-independent growth [ 28 ] .

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Functionally, USP37 depletion causes decreased cell proliferation measured by MTS, two-dimensional (2D) colony formation as well as three-dimensional (3D) anchorage- independent growth.

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Functionally, downregulated USP37 decreases cell proliferation and anchorage-independent growth [28].

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USP37 activates cell population proliferation.

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USP37 activates cell population proliferation. 6 / 6

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Depletion of USP37 also reduced cellular proliferation and led to increased sensitivity to agents that induce replication stress.

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USP37 promotes cell proliferation by stabilizing 14-3-3gamma.

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XREF_BIBR Therefore, it is possible that IH mediated miR-320b reduction in lung cancer cells resulted in the upregulation of USP37, which further promoted cancer cell proliferation, invasion, and survival.

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Notably, our results showed that overexpression of USP37, but not USP37 (C350S), enhanced the proliferation of cancer cells when 14-3-3gamma was co-transfected.

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Knockdown of USP37 inhibits cell proliferation and induces apoptosis To investigate the latent role of USP37 gene in the transformation of breast cancer cells , cell proliferation was examined by CCK-8 assay .

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Accumulating evidence has demonstrated that USP37 promotes lung cancer cell proliferation, migration, and invasion XREF_BIBR but inhibits lung cancer cell apoptosis in a deubiquitination dependent manner.

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USP37-C350S activates cell population proliferation. 1 / 1

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Notably, our results showed that overexpression of USP37, but not USP37 (C350S), enhanced the proliferation of cancer cells when 14-3-3gamma was co-transfected.

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X affects USP37

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X activates USP37.

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X activates USP37. 6 / 6

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Thus, we wondered if the effect of DUB inhibitor on SIRT7 protein levels observed in presence of HBx was dependent upon HBx mediated up-regulation of USP37.

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Ironically, Emi1 overexpression did not lead to USP37 accumulation thereby mitigating the possible role of Emi1 in HBx mediated USP37 stabilization.

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Many recent studies have highlighted the significant role of E3 ubiquitin ligases, deubiquitinases or substrate translocation between cell compartments, leading to substrate stability motivated us to explore the effect of HBx driven exodus of USP37 from the nucleus vis-a-vis its intracellular stability.

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HBx of HBV could upregulate USP37 transcripts in both hepatic and non-hepatic cells and also prevents USP37 from proteasomal degradation.

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The HBx dependent up-regulation of USP37 could be seen even in non hepatic cells such as HEK293T and U2OS.

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Conversely, HBx rescued USP37 from CDH1 mediated down-regulation similar to CDC6 but not the other CDH1 substrate, Geminin XREF_BIBR (XREF_FIG).

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X inhibits USP37.

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X inhibits USP37. 3 / 3

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HBx of HBV could upregulate USP37 transcripts in both hepatic and non-hepatic cells and also prevents USP37 from proteasomal degradation .

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As expected, overexpression of HBx unlike NESM mutant abrogated the interaction of USP37 with its cognate E3 ligases- CDH1 and beta-TrCP (XREF_FIG).

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HBx of HBV could upregulate USP37 transcripts in both hepatic and non-hepatic cells and also prevents USP37 from proteasomal degradation.

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X increases the amount of USP37.

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X increases the amount of USP37. 3 / 3

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HBx was also found to stimulate the gene transcription and protein expression of USP37.

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Thus, by stabilizing the expression of USP37, HBx promotes the accumulation of cyclin A to modulate cell cycle progression.

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HBx augments the expression of USP37.

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X deubiquitinates USP37.

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X leads to the deubiquitination of USP37. 1 / 1

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As HBx could effectively prevent the ubiquitination of USP37, we assessed the regulation of its E3 ubiquitin ligases- CDH1 and beta-TrCP in the presence of HBx.

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USP37 affects CDT1

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USP37 increases the amount of CDT1.

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USP37 increases the amount of CDT1. 5 / 5

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Moreover, previous evidence has shown that USP37 promotes the expression of CDT1.

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Using an overexpression screen of 78 human ubiquitin and ubiquitin-like hydrolases, Perez et al. reported that USP37 increases CDT1 levels when cells are exposed to DNA-damaging agents while USP37 depletion with siRNA decreases CDT1 protein levels [48].

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The results revealed that the overexpression of USP37 increased CDT1 protein levels and USP37 silencing decreased CDT1 expressions (XREF_FIG I and 5J).

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To understand whether the regulation of CDT1 expression by USP37 plays a role in lung cancer cell growth and invasion, the expressions of miR-320b and/or CDT1 in lung cancer cells (A549 and H1650) were altered.

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The results illustrated that USP37 knockdown significantly reduced CDT1 protein levels while lysosomal inhibitor (MG132) preserved the CDT1 protein (XREF_FIG M).

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USP37 activates CDT1.

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USP37 activates CDT1. 3 / 3

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Moreover , previous evidence has shown that USP37 promotes the expression of CDT1 .

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Thus, we hypothesized that USP37 may contribute to the tumorigenesis of lung cancer by regulating CDT1.

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Using an overexpression screen of 78 human ubiquitin and ubiquitin-like hydrolases , Perez et al. reported that USP37 increases CDT1 levels when cells are exposed to DNA-damaging agents while USP37 depletion with siRNA decreases CDT1 protein levels [ 48 ] .

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USP37 inhibits CDT1.

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USP37 inhibits CDT1. 1 / 1

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To explore whether USP37 mediates the proteasomal degradation of CDT1, we treated USP37 silencing cells with MG132 or dimethyl sulfoxide (DMSO) and detected the expression of CDT1 afterward.

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USP37 decreases the amount of CDT1.

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USP37 decreases the amount of CDT1. 1 / 1

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The results revealed that the overexpression of USP37 increased CDT1 protein levels and USP37 silencing decreased CDT1 expressions (XREF_FIG I and 5J).

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E2F1 affects USP37

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E2F1 decreases the amount of USP37.

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E2F1 decreases the amount of USP37. 7 / 7

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E2F1 increases the amount of USP37.

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E2F1 increases the amount of USP37. 1 / 1

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Not surprisingly, transactivation mutant of E2F1, E2F1 1-374 (DeltaC) is unable to stimulate the expression of USP37 gene.

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Mutated E2F1 increases the amount of USP37. 1 / 1

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Not surprisingly, transactivation mutant of E2F1, E2F1 1-374 (DeltaC) is unable to stimulate the expression of USP37 gene.

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E2F1 activates USP37.

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E2F1 activates USP37. 1 / 1

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In addition, E2F1 overexpression in U2OS cells increased both USP37 mRNA and USP37 protein.

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CDK2 affects USP37

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CDK2 activates USP37. 8 / 9

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Deubiquitinase USP37 is activated by CDK2 to antagonize APC (CDH1) and promote S phase entry [XREF_BIBR].

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Deubiquitinase USP37 is activated by CDK2 to antagonize APC (CDH1) and promote S phase entry.

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Since USP37 S 628 exists within a minimum CDK phosphorylation motif (S/T-P) (Dephoure et al., 2008), CDK2 interacts with USP37, and CDK2 is active in G1/S, we investigated whether CDK2 phosphorylates [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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There is positive reinforcement of this signaling mechanism because phosphorylation of Ser 628 by CDK2 and cyclin E and CDK2 and cyclin A complexes produces maximal USP37 activity, and USP37 activates[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Overexpression of CDK2 activating cyclin A or E increased USP37 activity toward HA-Ubi-VS, whereas cyclins B and D were without effect, suggesting that USP37 is one of several CDK2 substrates that int[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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We found this interesting because USP37 has been implicated in cell proliferation and transformation [ 6, 7 ] as well as in cell-cycle regulation, where during the G1/S transition, CDK2 phosphorylates[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry [ xref ].

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PLAGL2 affects USP37

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PLAGL2 increases the amount of USP37.

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PLAGL2 increases the amount of USP37. 6 / 6

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Besides, we showed that PLAGL2 directly activates USP37 expression, which targets Snail1 to proteasome ubiquitination degradation.

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Finally, PLAGL2 modulates SNAI1 stability by activating USP37 transcription.

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Moreover, silencing PLAGL2 decreased the mRNA level of USP37 in SGC7901 cells, whereas PLAGL2 overexpression increased the USP37 mRNA level in AGS cells.

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PLAGL2 modulates Snail1 stability by activating USP37 transcription.

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These results collectively suggest that PLAGL2 transcriptionally activates USP37 expression to increase Snail1 protein levels, which in turn mediates the proliferation, migration, and invasion of GC cells.

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PLAGL2 activated the transcription of deubiquitinase USP37, which then interacted with and deubiquitinated Snail1 protein directly.

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PLAGL2 deubiquitinates USP37.

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PLAGL2 leads to the deubiquitination of USP37. 1 / 1

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PLAGL2 activated the transcription of deubiquitinase USP37, which then interacted with and deubiquitinated Snail1 protein directly.

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PLAGL2 decreases the amount of USP37.

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Modified PLAGL2 decreases the amount of USP37. 1 / 1

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Moreover, silencing PLAGL2 decreased the mRNA level of USP37 in SGC7901 cells, whereas PLAGL2 overexpression increased the USP37 mRNA level in AGS cells.

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PLAGL2 activates USP37.

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PLAGL2 activates USP37. 1 / 1

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Although PLAGL2 does not function as a deubiquitinase to impede Snail1 ubiquitination, PLAGL2 transcriptionally activates USP37, which finally interacts with and deubiquitinates Snail1 directly.

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REST affects USP37

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REST increases the amount of USP37.

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REST increases the amount of USP37. 3 / 3

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Regulation of USP37 Expression by REST associated G9a dependent Histone Methylation.

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Notably, Das et al. reported that REST induces medulloblastoma oncogenesis by repressing USP37 transcription, thereby leading to low levels of the p27 tumor suppressor, which controls proliferation and cell cycle exit by inhibiting CDK1 in cerebellar progenitor cells.

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Like p27, a reciprocal association between USP37 and REST is present, and REST KD increases USP37 mRNA levels.

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REST decreases the amount of USP37.

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REST decreases the amount of USP37. 3 / 3

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REST also represses the transcription of the anti-proliferative deubiquitylase USP37, and drugs that reactivate USP37 expression may have therapeutic applications [XREF_BIBR].

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Previously, we observed that the expression of USP37 is transcriptionally repressed by the RE1 Silencing Transcription Factor (REST), which requires chromatin remodeling factors for its activity.

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Conversely, REST knockdown upregulated USP37 gene expression and promoted an increase in p27 protein levels.

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REST activates USP37.

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REST activates USP37. 2 / 2

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In medulloblastomas, REST expression could decrease cyclin dependent kinase (CDK) NIB and p27 (a CDK inhibitor) by repressing ubiquitin specific peptidase 37 (USP37), which could form a complex with p27 to promote its deubiquitination and stabilization, and resulting in blocked cell proliferation [XREF_BIBR].

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USP37 affects Neoplasm Invasiveness

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USP37 activates Neoplasm Invasiveness.

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In contrast , USP37 upregulation promotes EMT , migration , and invasion [ 39 ] .

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In contrast, USP37 upregulation promotes EMT, migration, and invasion [39].

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We previously demonstrated that ubiquitin carboxyl-terminal hydrolase 37 (UCH37), a member of the DUBs, promoted invasion and postoperative recurrence of HCC, and pre-mRNA processing factor 19 (Prp19) may function as its downstream effecter [XREF_BIBR].

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Further studies indicated that USP37 knockdown could inhibit the stemness, cell invasion and EMT in breast cancer via downregulation of Hh pathway.

30482232

USP37 inhibits Neoplasm Invasiveness.

| 1

USP37 inhibits Neoplasm Invasiveness. 1 / 1

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A study by Qin et al. reported that USP37 KD suppresses BC and BC stem cell migration and invasion by promoting the mesenchymal-epithelial transition (MET) by markedly reducing the SNAI1, N-cadherin, and vimentin expression and increasing the E-cadherin.

| PMC

USP37 affects BRCA1

| 7

USP37 activates BRCA1.

| 4

USP37 activates BRCA1. 4 / 4

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reach

Together, these results suggest that USP26 and USP37 promote the BRCA1 dependent loading of PALB2 and RAD51 by counteracting the repressive impact of RAP80 dependent BRCA1 sequestration and RAP80 dependent inhibition of end-resection during HR.

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In relation to its role maintaining chromosomal integrity, USP37 localizes to double-strand breaks and promotes BRCA1 inclusion into complexes responsible for homologous recombination 16.

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On the other hand, we also found that USP26 and USP37 promote the efficient association of BRCA1 with PALB2.

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Loss of USP26 or USP37 impairs HR by counteracting RAP80 dependent sequestration of BRCA1.

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USP37 inhibits BRCA1.

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USP37 inhibits BRCA1. 3 / 3

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We reasoned that USP26 and USP37 may antagonize the RAP80 dependent sequestration of BRCA1 by removing RNF8 and RNF168 mediated ubiquitylation and thereby promote HR.

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In agreement with this hypothesis, we found that USP26 or USP37 depletion inhibits the efficient association of BRCA1 with PALB2, a unique subunit of the BRCC complex.

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26101254

USP37 affects epithelial to mesenchymal transition

| 3 3

USP37 activates epithelial to mesenchymal transition. 6 / 6

| 3 3

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USP37 is a modulator of the epithelial-mesenchymal transition and metastasis .

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reach

Further studies indicated that USP37 knockdown could inhibit the stemness, cell invasion and EMT in breast cancer via downregulation of Hh pathway.

30482232

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USP37 knockdown inhibits stemness , cell invasion and EMT via Hedgehog signaling pathway in breast cancer .

| PMC

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Therefore , USP37 promotes EMT via the SHH pathway , and the signalling outcomes are determined by the balance of activated and inhibitory GLI1 proteins [ 39 ] .

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In contrast, USP37 upregulation promotes EMT, migration, and invasion [39].

| PMC

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Therefore, USP37 promotes EMT via the SHH pathway, and the signalling outcomes are determined by the balance of activated and inhibitory GLI1 proteins [39].

| PMC

USP37 affects homologous recombination

| 6

USP37 activates homologous recombination.

| 4

USP37 activates homologous recombination. 4 / 4

| 4

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Given that USP26 and USP37 are able to reverse RNF8/168 mediated ubiquitylation and promote HR, these enzymes would be ideal candidates to facilitate the repositioning of ubiquitylated substrates away from the DSB.

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A striking conclusion from our study is that both over-expression as well as knockdown of USP26 or USP37 impairs HR.

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Loss of USP26 and USP37 function markedly impairs the assembly of PALB2, RAD51 and efficient HR.

26101254

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Loss of USP26 or USP37 impairs HR by counteracting RAP80 dependent sequestration of BRCA1.

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USP37 inhibits homologous recombination.

| 2

USP37 inhibits homologous recombination. 2 / 2

| 2

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reach

We reasoned that USP26 and USP37 may antagonize the RAP80 dependent sequestration of BRCA1 by removing RNF8 and RNF168 mediated ubiquitylation and thereby promote HR.

26101254

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reach

Depletion of USP26 or USP37 disrupts the execution of HR and this effect is alleviated by the simultaneous depletion of RAP80.

26101254

USP37 affects MYC

| 3

USP37 activates MYC.

| 2

USP37 activates MYC. 2 / 4

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The overexpression of USP37 markedly increases c-Myc abundance by blocking its degradation, whereas the depletion of USP37 promotes c-Myc degradation and reduces c-Myc levels.

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XREF_BIBR - XREF_BIBR Moreover, the USP37 and USP36 can promote tumorigenesis by stabilizing c-Myc.

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USP37 decreases the amount of MYC.

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USP37 decreases the amount of MYC. 1 / 1

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The overexpression of USP37 markedly increases c-Myc abundance by blocking its degradation, whereas the depletion of USP37 promotes c-Myc degradation and reduces c-Myc levels.

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USP37 affects APC

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USP37 activates APC.

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USP37 activates APC. 3 / 3

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Other APC CDH1 substrates, including CDC20, CDC6, PLK1, Aurora kinase A, and SKP2, were not decreased by USP37 knockdown, indicating a specific effect of USP37 on cyclin A abundance.Coimmunoprecipitat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Deubiquitinase USP37 is activated by CDK2 to antagonize APC (CDH1) and promote S phase entry [XREF_BIBR].

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Deubiquitinase USP37 is activated by CDK2 to antagonize APC (CDH1) and promote S phase entry.

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USP37 inhibits APC.

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USP37 inhibits APC. 2 / 2

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Deubiquitinase USP37 is activated by CDK2 to antagonize APC (CDH1) and promote S phase entry.

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reach

Deubiquitinase USP37 is activated by CDK2 to antagonize APC (CDH1) and promote S phase entry [XREF_BIBR].

25972356

USP37 affects Cyclin

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USP37 activates Cyclin.

| 4

Mutated USP37 activates Cyclin. 2 / 2

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Reconstitution of an shRNA resistant KEN box-3 mutant USP37 in USP37-knockdown U2OS cells enables cyclin A to be accumulated again.

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USP37-FLAG, but not catalytic mutant USP37 C 350 S (hereafter called USP37DD for DUB-Dead), also increased endogenous cyclin A.

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USP37 activates Cyclin. 2 / 2

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In this regard, cyclin A2 degradation during interphase is specifically impeded by the deubiquitinating enzyme USP37 54, but this enzyme does not appear to antagonize cyclin B1 degradation.

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USP37 was shown to induce the stability of cyclin A by deubiquitination, resulting in an accumulation of cyclin A, which leads to the G1-S phase transition [XREF_BIBR].

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USP37 inhibits Cyclin.

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USP37 inhibits ubiquitinated Cyclin. 1 / 1

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Western blot analysis of cyclin A following immunoprecipitation of HA-ubiquitin-modified proteins from SDS and heat denatured lysates revealed that USP37, but not USP37DD, reduced the amount of ubiqui[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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TFDP1 affects USP37

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TFDP1 decreases the amount of USP37. 4 / 4

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No evidence text available

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

USP37 affects cell migration

| 4

USP37 inhibits cell migration.

| 2

USP37 inhibits cell migration. 2 / 2

| 2

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reach

Importantly, depletion of USP37 downregulates endogenous SNAI1 protein and suppresses cell migration, which can be reversed by re-expression of SNAI1.

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Indeed, USP37 KD reduces cell migration in transwell assays [62].

| PMC

USP37 activates cell migration.

| 2

USP37 activates cell migration. 2 / 2

| 2

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USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein

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Overexpression of wild-type USP37, but not its catalytically inactive mutant C350S, promotes cancer cell migration.

31911859

USP37 affects UIMC1

| 4

USP37 inhibits UIMC1.

| 2

USP37 inhibits UIMC1. 2 / 2

| 2

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reach

We reasoned that USP26 and USP37 may antagonize the RAP80 dependent sequestration of BRCA1 by removing RNF8 and RNF168 mediated ubiquitylation and thereby promote HR.

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26101254

USP37 activates UIMC1.

| 2

USP37 activates UIMC1. 2 / 2

| 2

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Together, this model may explain how USP26 and USP37 limit the repressive impact of RAP80 on HR.

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Loss of USP26 or USP37 impairs HR by counteracting RAP80 dependent sequestration of BRCA1.

26101254

Valproic acid affects USP37

3 |

Valproic acid decreases the amount of USP37. 3 / 3

3 |

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No evidence text available

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No evidence text available

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No evidence text available

23179753

Hsa-miR-19b-3p affects USP37

3 |

Hsa-miR-19b-3p decreases the amount of USP37. 3 / 3

3 |

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biopax:mirtarbase

No evidence text available

22473208

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No evidence text available

20371350

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No evidence text available

23313552

HNF4A affects USP37

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HNF4A decreases the amount of USP37. 3 / 3

3 |

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

Sodium arsenate affects USP37

3 |

Sodium arsenate increases the amount of USP37.

2 |

Sodium arsenate increases the amount of USP37. 2 / 2

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No evidence text available

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No evidence text available

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Sodium arsenate decreases the amount of USP37.

1 |

Sodium arsenate decreases the amount of USP37. 1 / 1

1 |

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ctd

No evidence text available

21795629

USP37 affects doxorubicin

| 3

USP37 activates doxorubicin.

| 2

USP37 activates doxorubicin. 2 / 2

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USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin.

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The expression levels of USP37 in both MCF-7 and MCF-7 and ADR cells increased significantly with the exposure to adriamycin in a dose dependent manner.

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USP37 inhibits doxorubicin.

| 1

USP37 inhibits doxorubicin. 1 / 1

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It was verified by the observation that USP37 downregulation elevated the inhibitory effects of adriamycin on breast cancer cells, suppressed cell proliferation caused by cell cycle arrest in G1/S transition, as well as induced apoptosis.

33390801

USP37 affects Ubiquitin

| 3

USP37 inhibits Ubiquitin.

| 2

USP37 inhibits Ubiquitin. 2 / 2

| 2

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USP26 or USP37 antagonize ubiquitin dependent spreading of RAP80-BRCA1.

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Previous studies reported that USP37 increased the Warburg effect and cell viability by repressing ubiquitin mediated degradation of c-Myc XREF_BIBR.

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USP37 activates Ubiquitin.

| 1

USP37 activates Ubiquitin. 1 / 1

| 1

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These results suggested that the UIMs in USP37 contribute to the full enzymatic activity, but not ubiquitin chain substrate specificity, of USP37 possibly by holding the ubiquitin chain substrate in the proximity of the catalytic core.

24324262

USP37 affects Neoplasm Metastasis

| 1 2

USP37 activates Neoplasm Metastasis.

| 1 1

USP37 activates Neoplasm Metastasis. 2 / 2

| 1 1

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eidos

USP37 is a modulator of the epithelial-mesenchymal transition and metastasis .

| PMC

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This was further validated in an orthotopic mouse model in which USP37 depletion reduces primary kidney tumorigenesis and decreases lung metastasis.

| PMC

USP37 inhibits Neoplasm Metastasis.

| 1

USP37 inhibits Neoplasm Metastasis. 1 / 1

| 1

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reach

Depletion of USP37 impairs ccRCC growth in 2D and 3D growth assays and in vivo kidney tumorigenesis and lung metastasis [XREF_BIBR]; therefore, inhibiting USP37 could be a viable therapeutic approach in VHL deficient or HIF-2alpha-dependent tumors.

| PMC

USP37 affects CDKN1B

| 3

USP37 activates CDKN1B.

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USP37 activates CDKN1B. 2 / 2

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Addition of USP37 to a reaction mix containing HA-ubiquitin and Myc-p27 caused a substantial increase in the 27kD form of p27 and a corresponding decrease in the slower migrating forms of the protein relative to reactions containing USP37 and a protease inhibitor N-ethyl maleimide (NEM) or USP37 C350-S or USP1 (XREF_FIG).

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USP37 inhibits CDKN1B.

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USP37 inhibits CDKN1B. 1 / 1

| 1

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Knockdown of REST and USP37 prevented p27 stabilization and blocked the diminution in proliferative potential that normally accompanied REST loss.

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CDH1 affects USP37

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CDH1 inhibits USP37. 2 / 2

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Overexpression of CDH1, but not CDC20, beta-TRCP1, or beta-TRCP2, decreased endogenous USP37 in 293T cells.

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CDH1 promoted USP37 degradation except when the KEN box-3 was mutated.

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CDH1 bound to APC inhibits USP37. 1 / 1

| 1

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Since USP37 is degraded by the proteasomal machinery after ubiquitination by SCF and beta-TrCP and APC and CDH1 complex, we wondered if USP37 could escape proteasomal degradation machinery in the presence of HBx.

25347529

USP37 affects USP37

| 3

USP37 inhibits USP37.

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USP37 inhibits USP37. 1 / 1

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Ambiguously, the transcription of USP37 is suppressed in medulloblastoma cells through the activity of RE1 silencing transcription factor to prevent the USP37 mediated stabilization of the cyclin dependent kinase inhibitor p27, which is known to act as a negative regulator of cell cycle XREF_BIBR.

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USP37 increases the amount of USP37.

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USP37 increases the amount of USP37. 1 / 1

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Besides, the overexpression of CI USP37 significantly increased the ubiquitination level of USP37 (XREF_FIG N).

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USP37 activates USP37.

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USP37 activates USP37. 1 / 1

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Hsa-miR-30c-5p affects USP37

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Hsa-miR-30c-5p decreases the amount of USP37. 2 / 2

2 |

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biopax:mirtarbase

No evidence text available

22473208

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No evidence text available

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Hsa-miR-19a-3p affects USP37

2 |

Hsa-miR-19a-3p decreases the amount of USP37. 2 / 2

2 |

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biopax:mirtarbase

No evidence text available

23313552

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No evidence text available

22473208

USP37 affects ZBTB16

| 2

USP37 activates ZBTB16. 2 / 2

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It was reported that USP37 induced the stability of the oncogenic fusion protein PLZF and RARA.

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Furthermore, overexpression or depletion of USP37 caused an increase or decrease of PLZF and RARA protein half-life, correlating with down- or upregulation of PLZF and RARA poly-ubiquitination, respectively.

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USP37 affects WAPL

| 2

USP37 activates WAPL. 2 / 2

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Given the critical role of WAPL in the prophase pathway, it will be interesting to discern whether USP37 contributes to other WAPL dependent processes, such as chromatin structure or protecting cohesi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Depletion of USP37 reduces the stability of chromatin associated WAPL and increases the fraction of WAPL that is more heavily ubiquitylated in mitosis.

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USP37 affects RARA

| 2

USP37 activates RARA. 2 / 2

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It was reported that USP37 induced the stability of the oncogenic fusion protein PLZF and RARA.

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23208507

USP37 affects RAD51

| 2

USP37 activates RAD51. 2 / 2

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Loss of USP26 and USP37 function markedly impairs the assembly of PALB2, RAD51 and efficient HR.

26101254

USP37 affects PALB2

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USP37 activates PALB2. 2 / 2

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Loss of USP26 and USP37 function markedly impairs the assembly of PALB2, RAD51 and efficient HR.

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26101254

USP37 affects MITF

| 1 1

USP37 inhibits MITF. 2 / 2

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An RNAi screen in HeLa cells of 296 genes that increase the MI revealed that depletion of USP37 markedly increases the MI, suggesting that it plays a role in mitotic progression [76].

| PMC

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eidos

An RNAi screen in HeLa cells of 296 genes that increase the MI revealed that depletion of USP37 markedly increases the MI , suggesting that it plays a role in mitotic progression [ 76 ] .

| PMC

USP37 affects EPAS1

| 1 1

USP37 activates EPAS1. 2 / 2

| 1 1

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As a result, USP37 promotes HIF2alpha protein stability in an enzymatically dependent manner, and depletion of USP37 leads to HIF2alpha down-regulation in ccRCC.

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Among these DUBs , USP37 induced the most significant increase in HIF2alpha levels ( Fig. 2D ) .

| PMC

USP37 affects Carcinogenesis

| 1 1

USP37 activates Carcinogenesis. 2 / 2

| 1 1

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This was further validated in an orthotopic mouse model in which USP37 depletion reduces primary kidney tumorigenesis and decreases lung metastasis.

| PMC

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eidos

207 In addition to Fbw7 , other E3 ligases , such as beta-TrCP1 , CHIP and FBXO32 , can also ubiquitinate c-Myc , mediate its subsequent degradation and inhibit tumorigenesis.208-210 Moreover , the USP37 and USP36 can promote tumorigenesis by stabilizing c-Myc.211 ,212 By mass spectrometry , SUMO ligase protein inhibitor of activated STAT ( PIAS ) and Sentrin-specific protease 7 ( SENP7 ) were also found to control the SUMOylation of c-Myc at K326 and regulate its ubiquitination and degradation ( Fig. 2c ) .213 Ubiquitination regulates p53 p53 , one of the most important tumor suppressors , works in multiple cellular processes , such as cell cycle regulation , DNA repair and apoptosis .

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USP37 affects CDH1

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USP37 inhibits CDH1. 2 / 2

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| PMC

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However, HBx escorts USP37 from the nucleus, downregulates CDH1, and prevents its SCF mediated degradation via increased CDK2-mediated phosphorylation [24].

| PMC

TFDP2 affects USP37

2 |

TFDP2 decreases the amount of USP37. 2 / 2

2 |

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

RB1 affects USP37

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RB1 decreases the amount of USP37. 2 / 2

2 |

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

NRF1 affects USP37

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NRF1 decreases the amount of USP37. 2 / 2

2 |

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal affects USP37

| 2

N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal activates USP37. 2 / 2

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In contrast, USP37 remained constant in nocodazole synchronized U2OS cells treated with MG132.

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For this purpose, cells were transfected with HA-14-3-3gamma, and His Ubiquitin, with or without Myc-Usp37 and treated with MG132 before harvesting.

26427597

FBXO5 affects USP37

| 1 1

FBXO5 activates USP37. 2 / 2

| 1 1

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Accumulation of APC complex substrate E2F transcription factor targets EMI1, which completely inhibits APC and induces USP37 in the G1 phase (Fig. 1).

| PMC

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Accumulation of APC complex substrate E2F transcription factor targets EMI1 , which completely inhibits APC and induces USP37 in the G1 phase ( Fig. 1 ) .

| PMC

E3_Ub_ligase affects USP37

| 2

E3_Ub_ligase activates USP37. 2 / 2

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E3 ligases that are active during exit from mitosis and therefore might target USP37 for degradation include beta-TRCP1, beta-TRCP2, APC CDC20, and APC CDH1 (Frescas and Pagano, 2008; Peters, 2002).

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The dichotomy in the action of two E3 ligases targeting USP37 further inspired us to investigate the possibility of direct or indirect interaction between HBx and USP37 which could reveal a bigger role of HBx in protection of USP37.

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E2F4 affects USP37

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E2F4 decreases the amount of USP37. 2 / 2

2 |

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biopax:msigdb

No evidence text available

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biopax:msigdb

No evidence text available

Atrazine affects USP37

2 |

Atrazine increases the amount of USP37.

1 |

Atrazine increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

25929836

Atrazine decreases the amount of USP37.

1 |

Atrazine decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

22378314

USP37 affects proteolysis

| 1 1

USP37 inhibits proteolysis.

| 1

USP37 inhibits proteolysis. 1 / 1

| 1

➶

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Moreover , knockdown of USP37 increases BLM polyubiquitination , accelerates its proteolysis , and impairs its function in DNA damage response .

34606619

USP37 activates proteolysis.

| 1

USP37 activates proteolysis. 1 / 1

| 1

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Ubiquitin carboxyl-terminal hydrolase 37 (UCH37, also called UCHL5), a member of the deubiquitinating enzymes, can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain.

23725108

USP37 affects cell differentiation

| 2

USP37 inhibits cell differentiation.

| 1

USP37 inhibits cell differentiation. 1 / 1

| 1

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Unexpectedly, wild type USP37 expression also induced the expression of REST-target neuronal differentiation genes even though REST levels were unaffected.

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USP37 activates cell differentiation.

| 1

USP37 activates cell differentiation. 1 / 1

| 1

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22665064

USP37 affects SNAI1

| 2

USP37 inhibits SNAI1.

| 1

USP37 inhibits SNAI1. 1 / 1

| 1

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Importantly, depletion of USP37 downregulates endogenous SNAI1 protein and suppresses cell migration, which can be reversed by re-expression of SNAI1.

31911859

USP37 activates SNAI1.

| 1

USP37 activates SNAI1. 1 / 1

| 1

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USP37 Promotes Lung Cancer Cell Migration by Stabilizing Snail Protein

31998374

USP37 affects REST

| 2

USP37 increases the amount of REST.

| 1

Modified USP37 increases the amount of REST. 1 / 1

| 1

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Unexpectedly, Q-RT-PCR analyses showed that WT USP37 expression promoted a 2.7-8 fold increase in expression of the REST target genes Syn1, BDNF and SCG10 respectively, relative to vector transfected cells.

22665064

USP37 activates REST.

| 1

USP37 activates REST. 1 / 1

| 1

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In contrast, ectopic expression of a USP37 transgene carrying a mutation in a conserved cysteine residue failed to rescue REST dependent effects on p27, cell proliferation and neuronal differentiation.

22665064

USP37 affects Cell Survival

| 2

USP37 inhibits Cell Survival.

| 1

USP37 inhibits Cell Survival. 1 / 1

| 1

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The depletion of USP37 reduced the cell viability compared with a control.

26427597

USP37 activates Cell Survival.

| 1

USP37 activates Cell Survival. 1 / 1

| 1

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Previous studies reported that USP37 increased the Warburg effect and cell viability by repressing ubiquitin mediated degradation of c-Myc XREF_BIBR.

33391500

Neoplasms affects USP37

| 2

Neoplasms inhibits USP37.

| 1

Neoplasms inhibits USP37. 1 / 1

| 1

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Furthermore, miR-320b overexpression reduces IH-induced tumor growth by promoting USP37 downregulation.

| PMC

Neoplasms activates USP37.

| 1

Neoplasms activates USP37. 1 / 1

| 1

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Furthermore, miR-320b overexpression reduces IH-induced tumor growth by promoting USP37 downregulation.

| PMC

APC_C affects USP37

| 2

APC_C inhibits USP37.

| 1

APC_C bound to CDH1 inhibits USP37. 1 / 1

| 1

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USP37 was postulated to directly bind and stabilize cyclin A by stimulating its deubiquitination, promoting its accumulation and progression to G /S.Interestingly, the APC–CDH1 complex degrades USP37 in late mitosis by targeting its KEN box degron.

| PMC

APC_C activates USP37.

| 1

APC_C activates USP37. 1 / 1

| 1

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The inactivation of APC and C-CDH 1 is reinforced through the ubiquitin dependent degradation of CDH1 in S phase by the SKP1-Cullin-F-box (SCF) family ubiquitin ligase, SCF-cyclin F, as well as through deubiquitination of the critical APC and C-CDH 1 target cyclin A2 in late G1 and S phases by the E2F induced deubiquitinase USP37.

33166394

Vorinostat affects USP37

| 1

Vorinostat activates USP37. 1 / 1

| 1

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reach

To ask if HDAC inhibition is sufficient for USP37 upregulation, DAOY, D283 and UW426 cells were treated with either SAHA or MS-275 for 6-24 hrs and USP37 gene expression was measured by Q-RT-PCR.

28483947

Vincristine affects USP37

1 |

Vincristine decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

23649840

Vinclozolin affects USP37

1 |

Vinclozolin increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

23555832

Tungsten affects USP37

1 |

Tungsten decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

30912803

Trimellitic anhydride affects USP37

1 |

Trimellitic anhydride increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

19042947

Tetrachloromethane affects USP37

1 |

Tetrachloromethane increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

31150632

Succimer affects USP37

1 |

Succimer decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

26378955

Mono(2-ethylhexyl) phthalate affects USP37

1 |

Mono(2-ethylhexyl) phthalate decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

31059758

Methyl methanesulfonate affects USP37

1 |

Methyl methanesulfonate increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

23649840

Magnetite nanoparticle affects USP37

1 |

Magnetite nanoparticle decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

26378955

Lipopolysaccharide, E coli O55-B5 affects USP37

1 |

Lipopolysaccharide, E coli O55-B5 decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

24972896

Leflunomide affects USP37

1 |

Leflunomide increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

28988120

Jinfukang affects USP37

1 |

Jinfukang decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

27392435

Hsa-miR-891a-5p affects USP37

1 |

Hsa-miR-891a-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-8060 affects USP37

1 |

Hsa-miR-8060 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-6894-3p affects USP37

1 |

Hsa-miR-6894-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-6833-3p affects USP37

1 |

Hsa-miR-6833-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-6832-3p affects USP37

1 |

Hsa-miR-6832-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-6828-5p affects USP37

1 |

Hsa-miR-6828-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-6820-3p affects USP37

1 |

Hsa-miR-6820-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22100165

Hsa-miR-6809-3p affects USP37

1 |

Hsa-miR-6809-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-616-3p affects USP37

1 |

Hsa-miR-616-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-606 affects USP37

1 |

Hsa-miR-606 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-5580-5p affects USP37

1 |

Hsa-miR-5580-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-548av-3p affects USP37

1 |

Hsa-miR-548av-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-5003-3p affects USP37

1 |

Hsa-miR-5003-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-4775 affects USP37

1 |

Hsa-miR-4775 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-4772-3p affects USP37

1 |

Hsa-miR-4772-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-4768-5p affects USP37

1 |

Hsa-miR-4768-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-4763-5p affects USP37

1 |

Hsa-miR-4763-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-4753-3p affects USP37

1 |

Hsa-miR-4753-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-4709-3p affects USP37

1 |

Hsa-miR-4709-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-455-3p affects USP37

1 |

Hsa-miR-455-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-4501 affects USP37

1 |

Hsa-miR-4501 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22100165

Hsa-miR-4487 affects USP37

1 |

Hsa-miR-4487 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-4280 affects USP37

1 |

Hsa-miR-4280 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-4264 affects USP37

1 |

Hsa-miR-4264 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-3591-5p affects USP37

1 |

Hsa-miR-3591-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-32-3p affects USP37

1 |

Hsa-miR-32-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-3164 affects USP37

1 |

Hsa-miR-3164 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22100165

Hsa-miR-3119 affects USP37

1 |

Hsa-miR-3119 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-3118 affects USP37

1 |

Hsa-miR-3118 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22100165

Hsa-miR-30e-5p affects USP37

1 |

Hsa-miR-30e-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22473208

Hsa-miR-30d-5p affects USP37

1 |

Hsa-miR-30d-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22473208

Hsa-miR-30b-5p affects USP37

1 |

Hsa-miR-30b-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22473208

Hsa-miR-30a-5p affects USP37

1 |

Hsa-miR-30a-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22473208

Hsa-miR-302d-5p affects USP37

1 |

Hsa-miR-302d-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-302b-5p affects USP37

1 |

Hsa-miR-302b-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-miR-215-3p affects USP37

1 |

Hsa-miR-215-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-1910-5p affects USP37

1 |

Hsa-miR-1910-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-191-5p affects USP37

1 |

Hsa-miR-191-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23313552

Hsa-miR-185-3p affects USP37

1 |

Hsa-miR-185-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-142-3p affects USP37

1 |

Hsa-miR-142-3p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23592263

Hsa-miR-134-5p affects USP37

1 |

Hsa-miR-134-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

22100165

Hsa-miR-130b-5p affects USP37

1 |

Hsa-miR-130b-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23824327

Hsa-let-7e-5p affects USP37

1 |

Hsa-let-7e-5p decreases the amount of USP37. 1 / 1

1 |

➶

biopax:mirtarbase

No evidence text available

23622248

Hexabromocyclododecane affects USP37

1 |

Hexabromocyclododecane decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

29177809

Haloperidol affects USP37

1 |

Haloperidol increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

29458080

Genistein affects USP37

1 |

Genistein increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

24552547

Ethyl methanesulfonate affects USP37

1 |

Ethyl methanesulfonate increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

23649840

Dorsomorphin affects USP37

1 |

Dorsomorphin increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

30157643

Diisobutyl phthalate affects USP37

1 |

Diisobutyl phthalate decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

29458080

Chlordecone affects USP37

1 |

Chlordecone increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

29458080

Bleomycin A5 affects USP37

1 |

Bleomycin A5 decreases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

21040473

ZEB1 affects USP37

1 |

ZEB1 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

ZBTB16 affects USP37

| 1

ZBTB16 increases the amount of USP37. 1 / 1

| 1

➶

reach

Interestingly, PLZF but not RARα levels are elevated in response to USP37 overexpression.

| PMC

Ubiquitin affects USP37

| 1

Ubiquitin activates USP37. 1 / 1

| 1

➶

reach

Since, USP37 is targeted by both these ubiquitin ligases and HBx chaperoned USP37 out of the nucleus, we wondered if it was safeguard mechanism to prevent the ubiquitination and degradation of USP37.

25347529

USP37 affects sub

| 1

USP37 activates sub. 1 / 1

| 1

➶

reach

Subsequent phosphorylation of USP37 by either CDK2 and cyclin E or CDK2 and cyclin A triggers its full DUB activity.

21596315

USP37 affects smoothened signaling pathway

| 1

USP37 activates smoothened signaling pathway. 1 / 1

| 1

➶

eidos

USP37 mediates hedgehog signaling pathway through stabilizing components such as Smo and GLI-1 .

32426267

USP37 affects response to drug

| 1

USP37 activates response to drug. 1 / 1

| 1

➶

reach

These findings provide early evidence that USP37 modulates drug resistance.

| PMC

USP37 affects protein folding

| 1

USP37 activates protein folding. 1 / 1

| 1

➶

reach

Additionally, it is important to note that the introduction of a conserved cysteine residue in USP37 may have caused a change in protein folding and promoted its inactivation.

22665064

USP37 affects mesenchymal to epithelial transition

| 1

USP37 inhibits mesenchymal to epithelial transition. 1 / 1

| 1

➶

reach

| PMC

USP37 affects helicase

| 1

USP37 activates helicase. 1 / 1

| 1

➶

reach

Notably, Cdt1 ubiquitination can be reversed through the function of the ubiquitin hydrolase USP37, whose activity stabilizes Cdt1 and promotes helicase loading.

28094588

USP37 affects complex assembly

| 1

USP37 inhibits complex assembly. 1 / 1

| 1

➶

reach

These data suggest that USP26 and USP37 limit the magnitude of BRCA1-A complex assembly in DSB neighboring chromatin by counteracting RNF168 mediated H2A ubiquitylation.

26101254

USP37 affects cisplatin

| 1

USP37 inhibits cisplatin. 1 / 1

| 1

➶

reach

Additionally, USP37 knockdown inhibited tumorigenicity and increased anticancer effect of cisplatin in vivo.

30482232

USP37 affects chromosome segregation

| 1

USP37 activates chromosome segregation. 1 / 1

| 1

➶

reach

Therefore, in addition to a role in sister chromatid resolution, both USP37 and WAPL contribute to normal chromosome segregation and bioriented kinetochore-microtubule attachment.Given these similar p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

26299517

USP37 affects cell

| 1

USP37 activates cell. 1 / 1

| 1

➶

eidos

Functionally , USP37 depletion causes decreased cell proliferation measured by MTS , two-dimensional ( 2D ) colony formation as well as three-dimensional ( 3D ) anchorage - independent growth .

32461361

USP37 affects cell growth

| 1

USP37 inhibits cell growth. 1 / 1

| 1

➶

reach

Thus, we examined whether knock-down of USP37 decreased cancer cell growth by downregulation of 14-3-3gamma.

26427597

USP37 affects cell cycle

| 1

USP37 activates cell cycle. 1 / 1

| 1

➶

reach

Thus, by stabilizing the expression of USP37, HBx promotes the accumulation of cyclin A to modulate cell cycle progression.

30510918

USP37 affects attachment of spindle microtubules to kinetochore

| 1

USP37 activates attachment of spindle microtubules to kinetochore. 1 / 1

| 1

➶

reach

Additionally, identifying faulty kinetochore–microtubule attachments by error correction assay indicated that both USP37 and WAPL contribute to chromosomal segregation and bioriented kinetochore-microtubule attachment.

| PMC

USP37 affects apoptotic process

| 1

USP37 inhibits apoptotic process. 1 / 1

| 1

➶

reach

33898105

USP37 affects TCL1B

| 1

Modified USP37 increases the amount of TCL1B. 1 / 1

| 1

➶

reach

22665064

USP37 affects SMO

| 1

USP37 inhibits SMO. 1 / 1

| 1

➶

reach

Knockdown of USP37 significantly decreased hedgehog (Hh) pathway components Smo and Gli-1.

30482232

USP37 affects SIRT7

| 1

USP37 activates SIRT7. 1 / 1

| 1

➶

reach

However, expression of USP37 in IHH cells overexpressing HBx failed to further enhance the stability of SIRT7 (data not shown).

26442981

USP37 affects SEPTIN7

| 1

USP37 increases the amount of SEPTIN7. 1 / 1

| 1

➶

reach

USP37 promoted the expression of Cdc10 dependent transcript 1 (CDT1) in a deubiquitinase activity dependent manner.

33898105

USP37 affects S phase

| 1

USP37 activates S phase. 1 / 1

| 1

➶

reach

The deubiquitinase (DUB) USP37 has been found to stabilize cyclin A by removing the polyubiquitin from the latter and, hence, accelerates entry into S phase (Huang et al., 2011).

30510918

USP37 affects PRPF19

| 1

USP37 activates PRPF19. 1 / 1

| 1

➶

reach

26959880

USP37 affects Neoplasms

| 1

USP37 inhibits Neoplasms. 1 / 1

| 1

➶

reach

USP37 KD in MCF7 cells also increased sensitivity to chemotherapeutic agents such as cisplatin by decreasing the BCL2/BAX ratio and attenuating tumor growth in vivo [39].

| PMC

USP37 affects Medulloblastoma

| 1

USP37 activates Medulloblastoma. 1 / 1

| 1

➶

reach

| PMC

USP37 affects KITLG

| 1

USP37 inhibits KITLG. 1 / 1

| 1

➶

reach

However, HBx escorts USP37 from the nucleus, downregulates CDH1, and prevents its SCF mediated degradation via increased CDK2-mediated phosphorylation [24].

| PMC

USP37 affects Ile-His

| 1

USP37 inhibits Ile-His. 1 / 1

| 1

➶

reach

However, co-transfecting miR-320b mimic and USP37 failed to inhibit IH induced lung cancer cell invasion (XREF_FIG D and XREF_SUPPLEMENTARY B), indicating that miR-320b inhibited 6IH induced invasion in a USP37 dependent manner.

33898105

USP37 affects Hedgehog

| 1

USP37 activates Hedgehog. 1 / 1

| 1

➶

reach

USP37 mediates hedgehog signaling pathway through stabilizing components such as Smo and GLI-1.

32426267

USP37 affects GLI1

| 1

USP37 inhibits GLI1. 1 / 1

| 1

➶

reach

Knockdown of USP37 significantly decreased hedgehog (Hh) pathway components Smo and Gli-1.

30482232

USP37 affects E2F

| 1

USP37 increases the amount of E2F. 1 / 1

| 1

➶

sparser

Mechanistically It was seen that the E2F transcription factor activated USP37 transcription in late G1, Which results in accumulation of Cyclin A leading to G1/S transition.

| PMC

USP37 affects Drug Resistance

| 1

USP37 activates Drug Resistance. 1 / 1

| 1

➶

eidos

These findings provide early evidence that USP37 modulates drug resistance .

| PMC

USP37 affects DNA replication

| 1

USP37 inhibits DNA replication. 1 / 1

| 1

➶

reach

In addition, downregulation of USP37 reduces DNA replication fork speed.

27296872

USP37 affects DNA Breaks, Double-Stranded

| 1

USP37 activates DNA Breaks, Double-Stranded. 1 / 1

| 1

➶

reach

USP37 and USP26 are recruited to DSBs to remove RNF168-induced ubiquitin conjugates from the BRCA1-A complex, whereas loss of USP37 impairs DSB repair.

| PMC

USP37 affects Cohesin

| 1

USP37 activates Cohesin. 1 / 1

| 1

➶

reach

26299517

USP37 affects CHEK1

| 1

USP37 activates CHEK1. 1 / 1

| 1

➶

reach

The deubiquitinating enzyme USP37 enhances CHK1 activity to promote the cellular response to replication stress.

34509474

USP37 affects BCL2

| 1

USP37 activates BCL2. 1 / 1

| 1

➶

reach

USP37 KD in MCF7 cells also increased sensitivity to chemotherapeutic agents such as cisplatin by decreasing the BCL2/BAX ratio and attenuating tumor growth in vivo [39].

| PMC

USP37 affects BAX

| 1

USP37 activates BAX. 1 / 1

| 1

➶

reach

USP37 KD in MCF7 cells also increased sensitivity to chemotherapeutic agents such as cisplatin by decreasing the BCL2/BAX ratio and attenuating tumor growth in vivo [39].

| PMC

USP37 affects APC_C

| 1

USP37 inhibits APC_C. 1 / 1

| 1

➶

reach

Thus, Usp44 and Usp37 can restrict the activity of the major K11 specific ligase, the APC/C, in addition to deubiquitinating substrates modified with K11 linked chains.

21978762

USP37 affects 3D

| 1

USP37 inhibits 3D. 1 / 1

| 1

➶

reach

| PMC

USP37 affects 5-bromo-2'-deoxyuridine

| 1

USP37 activates 5-bromo-2'-deoxyuridine. 1 / 1

| 1

➶

reach

Bromodeoxyuridine (BrdU) incorporation into cells released from prometaphase was increased by USP37-FLAG, suggesting accelerated entry into S phase and a role for USP37 in regulating the G1/S transiti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

21596315

TCF3 affects USP37

1 |

TCF3 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

SP1 affects USP37

1 |

SP1 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

SNAI1 affects USP37

| 1

SNAI1 inhibits USP37. 1 / 1

| 1

➶

reach

Biologically, upregulated expression of USP37 promotes lung cancer cell migration, while depletion of Snail abolishes the effect of USP37.

31998374

RARA affects USP37

| 1

RARA activates USP37. 1 / 1

| 1

➶

reach

The retinoic acid receptor alpha (RARA) and the promyelocytic leukemia zinc finger (PLZF) fusion protein is a target of USP37 and the stabilization of PLZF and oncogenic transformation of acute promyelocytic leukemia cells has been attributed to USP37.

28483947

RAR affects USP37

| 1

RAR increases the amount of USP37. 1 / 1

| 1

➶

reach

Interestingly, PLZF but not RARα levels are elevated in response to USP37 overexpression.

| PMC

Plant Extracts affects USP37

1 |

Plant Extracts increases the amount of USP37. 1 / 1

1 |

➶

ctd

No evidence text available

23557933

PPARG affects USP37

1 |

PPARG decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

PPARA affects USP37

1 |

PPARA decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

PITX2 affects USP37

1 |

PITX2 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

USP37 is modified

| 1

USP37 is degraded. 1 / 1

| 1

➶

trips

Skp1-Cul1-F-box ubiquitin ligase (SCF(βTrCP))-mediated destruction of the ubiquitin-specific protease USP37 during G2-phase promotes mitotic entry.

23027877

NR2F2 affects USP37

1 |

NR2F2 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

Medulloblastoma affects USP37

| 1

Medulloblastoma inhibits USP37. 1 / 1

| 1

➶

reach

| PMC

Ile-His affects USP37

| 1

Ile-His activates USP37. 1 / 1

| 1

➶

reach

33898105

IRF1 affects USP37

1 |

IRF1 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

HIF1A affects USP37

1 |

HIF1A decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

GSK3B affects USP37

| 1

GSK3B activates USP37. 1 / 1

| 1

➶

reach

Besides, silencing of endogenous GSK-3beta impeded USP37 mediated stabilization of Snail1 in AGS cells.

33391500

ESRRA affects USP37

1 |

ESRRA decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

EHMT2 affects USP37

| 1

EHMT2 inhibits USP37. 1 / 1

| 1

➶

eidos

G9a reduces USP37 expression by promoting H3K9 mono - , di - , and trimethylation at its promoter .

| PMC

EGR2 affects USP37

1 |

EGR2 decreases the amount of USP37. 1 / 1

1 |

➶

biopax:msigdb

No evidence text available

EC 3.5.1.98 (histone deacetylase) inhibitor affects USP37

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EC 3.5.1.98 (histone deacetylase) inhibitor decreases the amount of USP37. 1 / 1

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The failure of the HDAC inhibitor, MS-275, to upregulate USP37 expression suggests that either HDAC1/2 activities are not necessary or are alone insufficient to de-repress USP37 expression (XREF_FIG).

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