USP44 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 44
HGNC Gene Symbol
USP44
Identifiers
hgnc:20064 NCBIGene:84101 uniprot:Q9H0E7
Orthologs
mgi:3045318 rgd:1308216
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP44
Number of Papers
51 retrieved on 2022-05-22

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 Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type
PLOD1 procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 -0.261
C2CD2L C2CD2 like -0.244
C6 complement C6 -0.243
ZBTB39 zinc finger and BTB domain containing 39 0.238
ABR ABR activator of RhoGEF and GTPase 0.236
KIAA0232 KIAA0232 -0.229
ZSCAN29 zinc finger and SCAN domain containing 29 0.226

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP44using 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

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP44 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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USP44 deubiquitinates CDC20. 10 / 14
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Moreover, Usp44, a ubiquitin isopeptidase, has been proposed to prevent the autoubiquitination of Cdc20 and maintain the Mad2-Cdc20 interaction during checkpoint activation.

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For example, USP44 directly deubiquitinates CDC20 and counteracts the APC driven disassembly of the Mad2 and CDC20 complex, which regulates the proper mitotic timing and the spindle checkpoint function 3.

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USP44 deubiquitinates the Cdc20 and prevents the APC driven disassembly of Mad2 and Cdc20 complex [XREF_BIBR].

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USP44 knockdown increased Cdc20 polyubiquitination and centrosomal Cdc20-APC activity in neurons, and correspondingly promoted the elaboration of dendrites.

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Knockdown of USP44 in neurons dramatically increased the polyubiquitination of Cdc20 and centrosomal Cdc20-APC activity, confirming that endogenous USP44 deubiquitinates Cdc20 in neurons (XREF_FIG).

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We have previously shown that USP44 deubiquitinates CDC20 to negatively regulate the anaphase promoting complex during the spindle checkpoint.

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USP44 deubiquitinates the APC coactivator Cdc20 both in vitro and in vivo, and thereby directly counteracts the APC driven disassembly of Mad2-Cdc20 complexes (discussed in an accompanying paper).

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Conversely, the deubiquitinating enzyme USP44 deubiquitinates Cdc20 and drives the assembly of the inhibitory SAC complexes.

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Interestingly, USP44 (ubiquitin specific protease 44) deubiquitinated Cdc20 and blocked premature activation of APC via stabilization of the APC-inhibitory Mad2 and Cdc20 complex.

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USP44 deubiquitinates Cdc20 and enables the stabilization of the inactive complex MAD2, CDC20, and APC/C [XREF_BIBR].
USP44 deubiquitinates Histone_H2B. 7 / 7
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However, whether USP44 directly deubiquitinates histone H2B or how its activity is targeted to chromatin are not known.

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Our results indicate that both the deubiquitination of histone H2B by USP44 and deacetylation of histone H3 by HDAC3 contribute to N-CoR mediated transcriptional repression (XREF_FIG).

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USP44 negatively regulates H2B ubiquitination during embryonic stem cell development [XREF_BIBR].

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Our results indicate that both the deubiquitination of histone H2B by USP44 and deacetylation of histone H3 by HDAC3 contribute to N-CoR-mediated transcriptional repression.

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However, whether USP44 directly deubiquitinates histone H2B or how its activity is targeted to chromatin is not known.

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As part of N-CoR, USP44 deubiquitinates H2B both in vivo and in vitro, and it contributes to N-CoR-mediated repression of target genes, including a genome integrated luciferase reporter (Vaquero et al[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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USP44 within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44 impairs the repressive activity of the N and CoR complex.
USP44 deubiquitinates DDB2. 6 / 6
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One possibility is that USP44 de-ubiquitinates DDB2 once it has been released, allowing it to be recycled back onto persisting CPDs.

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Consistent with the selective CPD repair defect in Usp44 null cells, we find that USP44 deubiquitinates the recognition protein DDB2 to facilitate its accumulation on DNA lesions and facilitate the subsequent recruitment of XPC.

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Ubiquitination of DDB2 was reversed by the inclusion of wild-type USP44 but not the catalytically inactive USP44C281A.

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USP44 Deubiquitinates and Prevents the Premature Degradation of DDB2.

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Here we show that the tumor suppressor USP44 directly deubiquitinates DDB2 to prevent its premature degradation and is selectively required for CPD repair.

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These data lead us to conclude that USP44 deubiquitinates DDB2 following UV exposure and prevents its premature degradation.
USP44 deubiquitinates FOXP3. 4 / 4
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To this end, we characterized the deubiquitination of FOXP3 by USP44 invitro in the presence of wild-type ubiquitin molecules and mutants lacking all but specific lysine residues.

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We therefore investigated whether or not USP44 co-operates with USP7 to deubiquitinate and preserve FOXP3.

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USP44 co-operates with USP7 to deubiquitinate FOXP3 and stabilize expression.

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Interestingly, USP44 co-operated with USP7 to deubiquitinate and stabilize FOXP3.
Modified USP44 leads to the deubiquitination of FOXP3. 2 / 2
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In these experiments, ubiquitination of FOXP3 was decreased by the co-expression of USP44 in the presence of wild-type ubiquitin.

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As expected, USP44 or USP7 expression alone reduced ubiquitination of FOXP3, while co-over-expression of both USP44 and USP7 almost completely eliminated FOXP3 polyubiquitination, suggesting a synergistic role of these two DUBs (Fig XREF_FIG C).
USP44 deubiquitinates Histone_H3. 2 / 2
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Our results indicate that both the deubiquitination of histone H2B by USP44 and deacetylation of histone H3 by HDAC3 contribute to N-CoR-mediated transcriptional repression.

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Our results indicate that both the deubiquitination of histone H2B by USP44 and deacetylation of histone H3 by HDAC3 contribute to N-CoR mediated transcriptional repression (XREF_FIG).
USP44 deubiquitinates MAD2L1. 2 / 2
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Knocking down USP14 arrests cell cycle at the G2/M phase and inhibits the proliferation and migration of breast cancer cells, USP44 deubiquitinates the APC-inhibitory Mad2 and Cdc20 complex, thereby preventing anaphase onset.

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USP39 deubiquitinates aurora B kinase maintaining spindle assembly checkpoint integrity [103] while USP44 stabilizes Mad2/Cdc20 complex inhibiting premature activation of the APC/CCdh1?complex
USP44 deubiquitinates EZH2. 1 / 1
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Another recent study found that USP44 deubiquitinates and stabilizes the expression an activity of the histone methyltransferase EZH2 in prostate tumor cells as well as oncogenic mutants of this epigenetic factor with pro tumor results.
USP44 leads to the deubiquitination of FBP1. 1 / 1
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Importantly, we revealed USP44 promoted FBP1 deubiquitination to increase FBP1 protein expression in pancreatic cancer, which might be one of the underlying mechanisms of USP44 impeding the progression of pancreatic cancer.
USP44 leads to the deubiquitination of PCNA. 1 / 1
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In undamaged cells, the deubiquitinating enzyme USP44 prevents PCNA ubiquitination and recruitment of error-prone DNA polymerases, and is proposed as a safeguard mechanism against the mutagenic effects of these polymerases.
USP44 deubiquitinates APC. 1 / 1
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USP44 deubiquitinates the APC coactivator Cdc20 both in vitro and in vivo, and thereby directly counteracts the APC driven disassembly of Mad2-Cdc20 complexes (discussed in an accompanying paper).
USP44 deubiquitinates ANGPTL4. 1 / 1
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As part of N-CoR, USP44 deubiquitinates H2B both in vivo and in vitro, and it contributes to N-CoR-mediated repression of target genes, including a genome integrated luciferase reporter (Vaquero et al[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP44 deubiquitinates POU5F1. 1 / 1
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USP44 deubiquitinates H2AC20. 1 / 1
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Both USP44 and USP29 promoted efficient deubiquitylation of histone H2A
USP44 deubiquitinates RNF168. 1 / 1
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Recruitment of USP44 to DNA damage sites was shown to be dependent on RNF168 and it was suggested that USP44 binds to and deubiquitinates RNF8 and RNF168 dependent ubiquitination at DSB, though it is [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP44 deubiquitinates H2BC21. 1 / 1
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USP44 deubiquitinates H2AC17. 1 / 1
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Review
USP44 deubiquitinates AXIN1. 1 / 1
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This indicates that USP44 deubiquitination of Axin1 increases beta-catenin degradation, inhibits Wnt and beta-catenin signaling, and affects CRC [XREF_BIBR].
USP44 deubiquitinates RNF8. 1 / 1
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Recruitment of USP44 to DNA damage sites was shown to be dependent on RNF168 and it was suggested that USP44 binds to and deubiquitinates RNF8 and RNF168 dependent ubiquitination at DSB, though it is [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP44 leads to the deubiquitination of Histone-H2A. 1 / 1
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USP44 promoted deubiquitination of histones H2A and H2B in vitro, localized to DNA damage foci, and inhibited the local formation of polyubiquitin chains at the sites of DNA damage.

Other Statements

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USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells.

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Taken together, this study demonstrates that USP44 inhibits proliferation while enhances apoptosis in CRC cells by inactivating Wnt and beta-catenin pathway via Axin1 deubiquitination.

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Collectively, these data indicated that USP44 inhibited proliferation while promoted apoptosis in CRC by inhibiting Wnt/β-catenin pathway.

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USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly.

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Depletion of USP44 inhibits proliferation, migration, and invasion in glioma cell lines.

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Here, we found that USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhanced apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC.

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Taken together, this study demonstrates that USP44 inhibits proliferation while enhances apoptosis in CRC cells by inactivating Wnt/β-catenin pathway via Axin1 deubiquitination.

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Collectively, these data indicated that USP44 inhibited proliferation while promoted apoptosis in CRC by inhibiting Wnt and beta-catenin pathway.

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Knockdown of USP44 inhibited proliferation, migration and invasion, induced apoptosis, and arrested cell cycle in G2/M phase in the established glioma cell lines.

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USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating Wnt and beta-catenin pathway via Axin1 deubiquitination.

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Overall, the difference derived from our experimental results indicated that the knockdown of USP44 inhibited proliferation, migration, and invasion in glioma cells.

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Indeed, knockdown of cyclin D1 or re-expression of USP44 reversed the proliferation of T80 and KLF8 cells back to the levels of the Mock cells (XREF_FIG).

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These results indicated that knockdown of USP44 inhibited the proliferation of glioma cells.

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These results suggested that knockdown of USP44 might inhibit glioma cell proliferation by arresting cell cycle in G2/M phase.

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USP44 hypermethylation promotes cell proliferation and metastasis in breast cancer.

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In established glioma cell lines, knockdown of USP44 inhibited the proliferation, migration, and invasion of the cells.

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XREF_BIBR The downregulation of miR-143-3p by circFoxo3 increased the level of USP44, which in turn promoted tumor cell proliferation.
USP44 affects FOXP3
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USP44 increases the amount of FOXP3.
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USP44 increases the amount of FOXP3. 4 / 4
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Our current findings suggest that USP44, another DUB without an appreciated immunoregulatory role, can act as a distinct force to support FOXP3 expression and both Treg phenotype and function.

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USP44 knockdown in Tregs decreased FOXP3 expression and disrupted patterns of Treg gene expression (i.e., suppression of IL-2 expression).

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Our present findings suggest that targeting factors such as USP44 and USP7 that promote FOXP3 expression at the protein level is a strategy that offers exciting possibilities for the fine tuning of immune responses in cancer.

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The ability of USP44 to promote FOXP3 expression was evident in our assessment of iTreg induction under limiting TGF-beta levels.
Modified USP44 increases the amount of FOXP3. 1 / 1
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Furthermore, increasing USP44 levels appeared to augment FOXP3 protein levels (Fig XREF_FIG B).
USP44 activates FOXP3.
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USP44 activates FOXP3. 4 / 4
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Combined USP7 and USP44 knockdown, however, even further enhanced FOXP3 degradation (Fig XREF_FIG D, left panel).

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These results suggest that Tregs devoid of USP44 mediated FOXP3 stabilization are ineffective suppressors of anti-tumor immune responses.

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Suspecting that USP44 targets FOXP3 for deubiquitination, we again utilized a co-IP approach to test this notion.

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USP44 promotes FOXP3 stabilization through deubiquitination.
USP44 inhibits FOXP3.
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USP44 inhibits FOXP3. 2 / 2
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In contrast, shRNA mediated knockdown of USP44 enhanced the disappearance of FOXP3 protein in Jurkat T cells (XREF_SUPPLEMENTARY).

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The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.
Mutated USP44 inhibits FOXP3. 1 / 1
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Furthermore, expression of a catalytically inactive mutant USP44 (" CS ") failed to prevent the modification of FOXP3 in this manner (Figs XREF_FIG A and XREF_FIG).

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Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown.

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Overexpression of USP44 leads to CIN.

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These results indicate that stable overexpression of USP44 leads to CIN in a human cell line.

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We conclude that USP44 levels are increased in T-ALL and that USP44 induced CIN may contribute to the pathogenesis of this disease.

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A previous study reported that overexpression of USP44 in mouse embryonic fibroblasts induced CIN 13.

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Finally, we investigated whether high USP44 expression caused CIN.

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USP44 is an important regulator in mitosis, and therefore suppression or overexpression of USP44 leads to aneuploidy, resulting in an induction of CIN.
TGFB affects USP44
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TGFB activates USP44.
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TGFB activates USP44. 4 / 4
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Notably , TGF-beta induces USP44 expression during iTreg differentiation .

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Suspecting that USP44 may be up-regulated in T cells by TGF-beta, we examined the promoter of the mouse and human USP44 gene using R-vista analysis software.

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Interestingly, ablating TGF-beta signaling in this system with an antibody neutralizing the cytokine reduced USP44 expression in cells stimulated with PMA and Iono without exogenous TGF-beta (Fig XREF_FIG C), suggesting that induced USP44 activity may be augmented by trace amounts of TGF-beta in the serum complemented culture media (RPMI) used in these experiments.

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During iTreg differentiation, TGF-beta signaling induces USP44 upregulation.
TGFB increases the amount of USP44.
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TGFB increases the amount of USP44. 3 / 3
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Notably, TGF-beta induces USP44 expression during iTreg differentiation.

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USP44 expression is up-regulated by TGF-beta during Treg differentiation.

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These findings strongly suggest that USP44 expression in Tregs is largely driven by TGF-beta and SMAD signaling.

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Depletion of USP44 significantly impaired the invasiveness of MDA-MB-231 cells in vitro and led to an increase of global H2Bub1 levels (XREF_FIG and XREF_SUPPLEMENTARY).

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The depletion of USP44 significantly impaired the invasiveness of MDA-MB-231 cells in vitro, and it led to an increase in global H2Bub1 levels.

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Depletion of USP44 inhibits proliferation, migration, and invasion in glioma cell lines.

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Knockdown of USP44 inhibited proliferation, migration and invasion, induced apoptosis, and arrested cell cycle in G2/M phase in the established glioma cell lines.
| 2

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Overall, the difference derived from our experimental results indicated that the knockdown of USP44 inhibited proliferation, migration, and invasion in glioma cells.

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In established glioma cell lines, knockdown of USP44 inhibited the proliferation, migration, and invasion of the cells.
USP44 affects CDC20
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USP44 activates CDC20. 1 / 4
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Moreover, Usp44 inhibits Cdc20 degradation and counteracts UbcH10 to decelerate the metaphase to anaphase transition [XREF_BIBR].
USP44 affects autophagy
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Moreover, downregulation of USP44 encoding gene blocks the induction of autophagy in mESCs (mouse embryonic stem cells) (XREF_FIG H).

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Knockdown of Usp44 results in the maintenance of H2Bub1 upon starvation and abolishes the change in expression of starvation induced autophagy related genes.

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Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance.
Modified USP44 inhibits autophagy. 1 / 1
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Indeed, depletion of USP44 expression by RNAi increased the levels of H2Bub1 and decreased the activity of autophagy significantly, as the levels of LC3B II were decreased and the p62 levels were increased after USP44 RNAi.
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USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating Wnt and beta-catenin pathway via Axin1 deubiquitination.

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Knockdown of USP44 inhibited proliferation, migration and invasion, induced apoptosis, and arrested cell cycle in G2/M phase in the established glioma cell lines.
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Down-regulation of USP44 promotes the apoptosis of glioma cells in vitro.

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Meanwhile, downregulating USP44 also induced apoptosis.
DNMT3B affects USP44
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DNMT3B inhibits USP44.
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DNMT3B inhibits USP44. 1 / 1
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Starvation induced USP44 up-regulation is mediated by DNMT3a and DNMT3b.
DNMT3B increases the amount of USP44.
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Modified DNMT3B increases the amount of USP44. 1 / 1
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The results showed that the depletion of DNMT3a and DNMT3b expression significantly increased the transcriptional levels of USP44, confirming that DNMT3a and DNMT3b are transcriptional silencers of the USP44 gene.
DNMT3B decreases the amount of USP44.
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DNMT3B decreases the amount of USP44. 1 / 1
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This result supports our biochemical analysis showing that DNMT3a and DNMT3b suppress the transcription of USP44 by regulating the DNA methylation of the gene.
DNMT3B activates USP44.
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DNMT3B activates USP44. 1 / 1
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Furthermore, the starvation induced H2Bub1 decrease and autophagy activation are shown to be regulated by the deubiquitinase USP44, which is transcriptionally targeted by the de novo DNA methyltransferases DNMT3a and DNMT3b.
DNMT3A affects USP44
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DNMT3A inhibits USP44.
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DNMT3A inhibits USP44. 1 / 1
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Starvation induced USP44 up-regulation is mediated by DNMT3a and DNMT3b.
DNMT3A increases the amount of USP44.
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Modified DNMT3A increases the amount of USP44. 1 / 1
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The results showed that the depletion of DNMT3a and DNMT3b expression significantly increased the transcriptional levels of USP44, confirming that DNMT3a and DNMT3b are transcriptional silencers of the USP44 gene.
DNMT3A decreases the amount of USP44.
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DNMT3A decreases the amount of USP44. 1 / 1
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This result supports our biochemical analysis showing that DNMT3a and DNMT3b suppress the transcription of USP44 by regulating the DNA methylation of the gene.
DNMT3A activates USP44.
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DNMT3A activates USP44. 1 / 1
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Furthermore, the starvation induced H2Bub1 decrease and autophagy activation are shown to be regulated by the deubiquitinase USP44, which is transcriptionally targeted by the de novo DNA methyltransferases DNMT3a and DNMT3b.
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Trichostatin A decreases the amount of USP44. 3 / 3
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USP44 depletion impairs differentiation and induction of RNF20 dependent genes.

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For instance, two histone directed DUBs, USP44 and USP22, are antagonistically regulated in their mRNA expression to ensure faithful stem cell differentiation [XREF_BIBR - XREF_BIBR].
Bisphenol A affects USP44
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Bisphenol A decreases the amount of USP44.
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Bisphenol A decreases the amount of USP44. 2 / 2
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Bisphenol A increases the amount of USP44.
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Bisphenol A increases the amount of USP44. 1 / 1
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USP44 affects cell cycle
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USP44 activates cell cycle.
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These results suggested that knockdown of USP44 might inhibit glioma cell proliferation by arresting cell cycle in G2/M phase.

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Our data showed that knockdown of USP44 arrested the cell cycle in G2/M phase concomitantly with the degradation of securin.
USP44 inhibits cell cycle.
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Knockdown of USP44 inhibited proliferation, migration and invasion, induced apoptosis, and arrested cell cycle in G2/M phase in the established glioma cell lines.
USP44 affects CTNNB1
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USP44 inhibits CTNNB1.
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USP44 inhibits CTNNB1. 2 / 2
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USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating Wnt and beta-catenin pathway via Axin1 deubiquitination.

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We found that USP44 overexpression increased Axin1 protein while decreased beta-catenin, c-myc and Cyclin D1 proteins, suggesting that USP44 inhibited the activation of Wnt and beta-catenin pathway.
USP44 decreases the amount of CTNNB1.
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Modified USP44 decreases the amount of CTNNB1. 1 / 1
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Increased expression of USP44 results in increased expression of Axin1, and decreased expressions of beta-catenin, c-Myc, and Cyclin D1.
USP44 affects Ubiquitin
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USP44 activates Ubiquitin.
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USP44 activates mutated Ubiquitin. 1 / 1
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Similarly, four of the seven possible single lysine residue variants (K6, K29, K33, and K63) did not allow FOXP3 deubiquitination by USP44 co-expression compared to wild-type and other ubiquitin mutants.
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This approach allowed us to identify the ubiquitin linkage type targeted by USP44.
USP44 inhibits Ubiquitin.
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It has been reported that USP44 inhibits the proteasome dependent degradation of CCNB1 by hydrolyzing its ubiquitin chain [XREF_BIBR].
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Valproic acid decreases the amount of USP44. 2 / 2
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Phenylmercury acetate decreases the amount of USP44. 2 / 2
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USP44 inhibited chromosome segregation errors independent of its role in the mitotic checkpoint by regulating centrosome separation, positioning, and mitotic spindle geometry.

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Surprisingly, they find that USP44 prevents chromosome segregation errors through a function independent of its previously identified role in the mitotic checkpoint.
USP44 affects Wnt
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USP44 inhibits Wnt. 2 / 2
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USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating Wnt and beta-catenin pathway via Axin1 deubiquitination.

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We found that USP44 overexpression increased Axin1 protein while decreased beta-catenin, c-myc and Cyclin D1 proteins, suggesting that USP44 inhibited the activation of Wnt and beta-catenin pathway.
USP44 affects RNF168
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USP44 inhibits RNF168. 2 / 2
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Similar to USP26 and USP37, two other DUBs, USP3 and USP44, were shown to reverse RNF168 induced chromatin ubiquitylation, thereby controlling the accumulation of BRCA1 and 53BP1 at sites of DNA damage.

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On the other hand, we also found 13 DUBs that were recruited to DNA damage sites but gave only marginal DSB repair defects upon siRNA depletion, including OTUB1, a negative regulator of the UBE2N (UBC13) ubiquitin E2 enzyme 24, USP44 that is reported to antagonize RNF168 dependent ubiquitylation 25, and OTUB2 that functions in repair-pathway choice 26 (XREF_FIG, XREF_FIG, and XREF_FIG), suggesting that some of the additional DUBs we identified might be negative DDR regulators and/or be involved in repair-pathway choice.
USP44 affects MAD2L1
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USP44 activates MAD2L1. 2 / 2
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In repeated experiments, we observed a modest but reproducible increase in the recovery of Mad2 with Cdc20, suggesting that excess Usp44 increases the association of Mad2 with Cdc20 (XREF_FIG).

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We find that high Usp44 promotes association of Mad2 with Cdc20 and reinforces the mitotic checkpoint.
USP44 affects JADE1
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USP44 increases the amount of JADE1. 2 / 2
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According to that study, the activation of stem cell transcription factor OCT4 pathway upregulated JADE1 gene expression along with stem cell factors NANOG, PHC1, USP44 and SOX2 60.

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According to that study, the activation of stem cell transcription factor OCT4 pathway upregulated JADE1 gene expression along with stem cell factors NANOG, PHC1, USP44 and SOX2 (Jung et al., 2010).
USP44 affects DDB2
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USP44 activates DDB2. 2 / 2
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USP44 Promotes the Accumulation of DDB2 on Damaged DNA.

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Data supporting this model is the finding that USP44 stimulates DDB2 accumulation directly upon DNA damage induction (XREF_FIG).
USP44 affects CCNB1
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USP44 activates CCNB1. 2 / 2
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It has been reported that USP44 inhibits the proteasome dependent degradation of CCNB1 by hydrolyzing its ubiquitin chain [XREF_BIBR].

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Taken together, these data suggest that exogenous Usp44 leads to increased cyclin B1 in G2 and prophase.
USP44 affects APC_C
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USP44 inhibits APC_C. 1 / 2
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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.

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The deubiquitinase Usp44 counteracts Ubch10 mediated ubiquitination of BubR1 and Mad2, and, accordingly, depletion of Usp44 abolishes SAC arrest even in the presence of normal checkpoint machinery.

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Although the precise mechanism (s) by which SAC requires phosphorylation is still unclear, it has been suggested that phosphorylation of Cdc20 and USP44 promotes SAC action XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR.
SMAD affects USP44
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SMAD inhibits USP44.
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SMAD inhibits USP44. 1 / 1
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In line with such a mechanism for USP44 induction in Tregs, and the findings obtained in our reporter system, T cells from mice genetically deficient in SMAD2 and SMAD3 fail to up-regulate USP44 under iTreg skewing conditions, and SMAD deficiency similarly abrogated USP44 up-regulation by iTregs (Fig XREF_FIG G).
SMAD increases the amount of USP44.
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SMAD increases the amount of USP44. 1 / 1
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These findings strongly suggest that USP44 expression in Tregs is largely driven by TGF-beta and SMAD signaling.
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Zinc sulfate decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
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Titanium dioxide increases the amount of USP44. 1 / 1
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ctd
No evidence text available
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Silicon dioxide increases the amount of USP44. 1 / 1
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ctd
No evidence text available
Propanal affects USP44
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Propanal increases the amount of USP44. 1 / 1
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ctd
No evidence text available
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ctd
No evidence text available
Kojic acid affects USP44
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Kojic acid decreases the amount of USP44. 1 / 1
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ctd
No evidence text available

ctd
No evidence text available
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Hydroperoxide increases the amount of USP44. 1 / 1
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ctd
No evidence text available
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Hsa-miR-6835-3p decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-5572 decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-450a-2-3p decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-4422 decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-4275 decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-4260 decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-335-5p decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-1276 decreases the amount of USP44. 1 / 1
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biopax:mirtarbase
No evidence text available
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Dorsomorphin decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
Cyclophosphamide hydrate decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
Cisplatin affects USP44
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Cisplatin increases the amount of USP44. 1 / 1
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ctd
No evidence text available
Bis(2-ethylhexyl) phthalate decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
All-trans-retinoic acid decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
Abrine affects USP44
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Abrine decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
VSX1 affects USP44
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VSX1 decreases the amount of USP44. 1 / 1
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biopax:msigdb
No evidence text available
USP44 affects peptidase
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We found that pretreatment of active USP44 in vitro, isolated from SAC arrested cells, with active 3F-Fcp1 substantially reduced USP44 ubiquitin peptidase activity, whereas pretreatment with the catalytic dead 3F-Fcp1-CD mutant had little effect (XREF_FIG).
USP44 affects pdaC
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USP44 inhibits pdaC. 1 / 1
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USP44 inhibit tumor cells progression and regulated gemcitabine resistance in PDAC.
USP44 affects nocodazole
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Over-expression of Usp44 reduces mitotic slippage in nocodazole.

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USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA.
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165 Mice with Treg specific USP44 deficiency display enhanced antitumor immunity, implicating USP44 as a potential target for cancer immunotherapy.
USP44 affects gemcitabine
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| 1

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USP44 inhibit tumor cells progression and regulated gemcitabine resistance in PDAC.
USP44 affects USP44
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USP44 bound to CTN activates USP44. 1 / 1
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The binding of USP44 with centrin, together with the predominant nuclear localization of USP44, led us to question the potential role of USP44 in NER.
USP44 affects USP3
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USP44 activates USP3. 1 / 1
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Similarly to USP3, USP44 can target the most common H2AK119ub mark and displace RNF168 and 53BP1 from IRIF [60,61].
USP44 affects RNF20
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USP44 inhibits RNF20. 1 / 1
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USP44 depletion impairs differentiation and induction of RNF20 dependent genes.
USP44 affects Proteasome
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It has been reported that USP44 inhibits the proteasome dependent degradation of CCNB1 by hydrolyzing its ubiquitin chain [XREF_BIBR].
USP44 affects PTTG1
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USP44 activates PTTG1. 1 / 1
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Securin is the catalytic substrate of USP44, knockdown of USP44 promotes degradation of securin.
USP44 affects Neoplasms
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These data reveal the requirement for highly regulated ubiquitin addition and removal in the recognition and repair of helix-distorting DNA damage and identify another mechanism by which USP44 protects genomic integrity and prevents tumors .

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USP44 hypermethylation promotes cell proliferation and metastasis in breast cancer.
USP44 affects NR1H2
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USP44 bound to CTN activates NR1H2. 1 / 1
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The binding of USP44 with centrin, together with the predominant nuclear localization of USP44, led us to question the potential role of USP44 in NER.
USP44 affects NCOR1
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USP44 inhibits NCOR1. 1 / 1
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USP44 enhances the repressive activity of N-CoR.
USP44 affects NCOR
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USP44 activates NCOR. 1 / 1
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The N and CoR complex is a well documented co-repressor for unliganded nuclear receptors, and our data demonstrate that USP44 contributes to NCoR mediated repression of the PPARdelta target gene Angptl4.
USP44 affects MYC
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Modified USP44 decreases the amount of MYC. 1 / 1
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Increased expression of USP44 results in increased expression of Axin1, and decreased expressions of beta-catenin, c-Myc, and Cyclin D1.
USP44 affects KLF8
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USP44 activates KLF8. 1 / 1
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Indeed, knockdown of cyclin D1 or re-expression of USP44 reversed the proliferation of T80 and KLF8 cells back to the levels of the Mock cells (XREF_FIG).
USP44 affects KAT5
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USP44 activates KAT5. 1 / 1
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Indeed, we found that USP44 can promote the stability of TIP60 in a dose dependent manner.
USP44 affects IL6
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USP44 increases the amount of IL6. 1 / 1
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However, USP44 silencing induced spindle multipolarity, abated VM, reduced transendothelial migration, and consequently decreased IL6 and IL8 levels in breast CSCs.
USP44 affects FBP1
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USP44 increases the amount of FBP1. 1 / 1
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Importantly, we revealed USP44 promoted FBP1 deubiquitination to increase FBP1 protein expression in pancreatic cancer, which might be one of the underlying mechanisms of USP44 impeding the progression of pancreatic cancer.
USP44 affects EZH2
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USP44 activates EZH2. 1 / 1
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Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2 dependent cancers.
USP44 affects Cyclin
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Modified USP44 decreases the amount of Cyclin. 1 / 1
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Increased expression of USP44 results in increased expression of Axin1, and decreased expressions of beta-catenin, c-Myc, and Cyclin D1.
USP44 affects CoR
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USP44 activates CoR. 1 / 1
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USP44 within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44 impairs the repressive activity of the N and CoR complex.
USP44 affects CXCL8
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USP44 increases the amount of CXCL8. 1 / 1
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However, USP44 silencing induced spindle multipolarity, abated VM, reduced transendothelial migration, and consequently decreased IL6 and IL8 levels in breast CSCs.
USP44 affects CRC
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USP44 inhibits CRC. 1 / 1
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Here, we found that USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhanced apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC.
USP44 affects BCL2
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USP44 activates BCL2. 1 / 1
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The blot density of Bax increased, while the blot density of Bcl-2 decreased in both U251-USP44-KD2 cells and A172-USP44-KD2 cells, which means down-regulating USP44 increased the ratio of Bax and Bcl -2.
USP44 affects BAX
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USP44 activates BAX. 1 / 1
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The blot density of Bax increased, while the blot density of Bcl-2 decreased in both U251-USP44-KD2 cells and A172-USP44-KD2 cells, which means down-regulating USP44 increased the ratio of Bax and Bcl -2.
USP44 affects AXIN1
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USP44 activates AXIN1. 1 / 1
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We found that USP44 overexpression increased Axin1 protein while decreased beta-catenin, c-myc and Cyclin D1 proteins, suggesting that USP44 inhibited the activation of Wnt and beta-catenin pathway.
USP44 affects APC
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USP44 inhibits APC. 1 / 1
| 1

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Interestingly, a groundbreaking study from Dr. Elledge 's group identified that the deubiquitinating enzyme USP44 (ubiquitin specific protease 44) prevents the premature activation of the APC through stabilization of the APC-inhibitory Mad2 and Cdc20 complex [XREF_BIBR].
UBE2C affects USP44
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UBE2C activates USP44. 1 / 1
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The proposed mechanism for this activity involves antagonistic activities of the Ub E2 conjugating enzyme UbcH10 and USP44 in which UbcH10 promotes checkpoint silencing, and USP44 promotes checkpoint maintenance.
STAT2 affects USP44
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STAT2 decreases the amount of USP44. 1 / 1
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biopax:msigdb
No evidence text available
STAT1 affects USP44
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STAT1 decreases the amount of USP44. 1 / 1
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biopax:msigdb
No evidence text available
SRY affects USP44
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SRY decreases the amount of USP44. 1 / 1
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biopax:msigdb
No evidence text available
PCB 180 affects USP44
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PCB 180 increases the amount of USP44. 1 / 1
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ctd
No evidence text available
KLF8 affects USP44
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KLF8 activates USP44. 1 / 1
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Zhao et al reported that KLF8 promoted proliferation in the human ovarian cell by up-regulating CCND1 and down-regulating USP44 expression [XREF_BIBR].
IRF1 affects USP44
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IRF1 decreases the amount of USP44. 1 / 1
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biopax:msigdb
No evidence text available
EZH2 affects USP44
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EZH2 activates USP44. 1 / 1
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We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44 mediated deubiquitination.
E2 affects USP44
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E2 activates USP44. 1 / 1
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The proposed mechanism for this activity involves antagonistic activities of the Ub E2 conjugating enzyme UbcH10 and USP44 in which UbcH10 promotes checkpoint silencing, and USP44 promotes checkpoint maintenance.
AR affects USP44
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AR decreases the amount of USP44. 1 / 1
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biopax:msigdb
No evidence text available
ANGPTL4 affects USP44
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ANGPTL4 activates USP44. 1 / 1
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Importantly, Angptl4 expression also was increased in Usp44 -null MEFs without or with ligand treatment compared with WT MEFs, indicating that USP44 is required for full repression of this N-CoR targe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
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ctd
No evidence text available
17alpha-ethynylestradiol decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
1-phenylpropan-2-amine decreases the amount of USP44. 1 / 1
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ctd
No evidence text available
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ctd
No evidence text available
2,4,4'-trichlorobiphenyl increases the amount of USP44. 1 / 1
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ctd
No evidence text available
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ctd
No evidence text available
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ctd
No evidence text available
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ctd
No evidence text available