USP6 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 6
HGNC Gene Symbol
USP6
Identifiers
hgnc:12629 NCBIGene:9098 uniprot:P35125
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP6
Number of Papers
199 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
CCDC144A coiled-coil domain containing 144A 0.301
CCDC144NL CCDC144A N-terminal pseudogene 0.299
TVP23B trans-golgi network vesicle protein 23 homolog B 0.285
GID4 GID complex subunit 4 homolog 0.281
SMCR8 SMCR8-C9orf72 complex subunit 0.262
MTRNR2L1 MT-RNR2 like 1 (pseudogene) 0.251
TNFSF12 TNF superfamily member 12 0.248

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP6using 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

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP6 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
RPLP1 ribosomal protein lateral stalk subunit P1 8.12e-01 1.69e-08 9.80e-05
RPS12 ribosomal protein S12 1.00e+00 2.86e-07 8.31e-04
RPSA ribosomal protein SA 9.26e-01 7.67e-07 1.49e-03
RPS27A ribosomal protein S27a 8.84e-01 1.67e-06 2.43e-03
RPS4X ribosomal protein S4 X-linked 9.69e-01 2.79e-06 3.24e-03
TPM3 tropomyosin 3 4.66e-01 5.19e-06 5.02e-03
RPL7A ribosomal protein L7a 6.94e-01 6.96e-06 5.78e-03
FCF1 FCF1 rRNA-processing protein 6.81e-01 3.33e-05 2.42e-02
RPS27AP16 RPS27A pseudogene 16 8.22e-01 3.88e-05 2.51e-02
MT1E metallothionein 1E 4.53e-01 9.83e-05 4.76e-02
RPL17 ribosomal protein L17 7.71e-01 9.62e-05 4.76e-02

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 USP6 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP6 deubiquitinates JAK1. 4 / 4
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We previously showed that ubiquitin specific protease 6 (USP6) directly deubiquitinates and stabilizes Jak1, thereby inducing an IFN signature in ES cells.

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To test whether USP6 can induce de-ubiquitination of Jak1 in vivo, HeLa cells were co-transfected with FLAG-Jak1, Myc-Ub, and HA-USP6 alleles.

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We found that USP6 directly deubiquitinated Jak1, leading to its stabilization and activation of STAT3.

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We found that USP6 directly deubiquitinated Jak1, leading to its stabilization and activation of STAT3.
USP6 deubiquitinates MMP9. 1 / 1
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USP6 deubiquitinates GRIN1. 1 / 1
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We also found that USP6 binds to and deubiquitinates NMDARs, thereby enhancing NMDAR stability.
Modified USP6 leads to the deubiquitination of JAK1. 1 / 1
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Co-expression of USP6, but not USP6 (short), completely abolished ubiquitination of Jak1 in vivo (XREF_FIG).
USP6 deubiquitinates JUN. 1 / 1
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Based on our data, USP6 is an enzyme that deubiquitinates c-Jun and regulates its downstream cellular functions.

Other Statements

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP6 affects NFkappaB
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Activation of NF-κB by USP6 was completely suppressed in these cells ( xref , left), in accordance with our previous results ( xref ).

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The findings above suggest that TRE17(long) may activate NF-κB by regulating nuclear translocation of an IκB-free population of p65.

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Here we demonstrate that TRE17 activates canonical p65-containing NF-κB through an atypical mechanism that is independent of IκB phosphorylation/degradation.

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In sum, these data indicate that TRE17(long) selectively activates classical NF-κB, consisting of either homo- or heterodimeric p65 complexes, in three different cell types.

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Our finding that TRE17 activates classical NF-κB in the absence of IκB degradation, and in a manner requiring both IKKα and IKKβ, adds to the growing list of stimuli that activate NF-κB through mechanisms distinct from simplified depiction of the classical pathway ( xref ; xref ).

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IκB-SR completely abrogated activation of NF-κB by TRE17 as determined by EMSA ( xref ).

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We previously reported that USP6 activates NF-kappaB, and that NF-kappaB plays an essential role in USP6 mediated transformation.

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TRE17 activates canonical NF-κB independently of IκB phosphorylation and degradation.

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We recently reported that TRE17 activates NF-κB, in a manner dependent on its USP activity ( xref ).

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Optimal activation of NF-κB by TRE17 requires both catalytic subunits of IKK, distinguishing its mechanism from the classical and non-canonical pathways, which require either IKKβ or IKKα, respectively.
USP6 affects STAT3
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USP6 activates STAT3. 10 / 15
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Jak1 in this clone was reduced to levels approximating those in control NIH3T3 cells (XREF_SUPPLEMENTARY), demonstrating that upregulation of Jak1 by USP6 is required for full activation of STAT3 by USP6.

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Jak1 in this clone was reduced to levels approximating those in control NIH3T3 cells ( xref ), demonstrating that upregulation of Jak1 by USP6 is required for full activation of STAT3 by USP6.

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USP6 activates STAT3 in cellular models and USP6 translocated tumors.

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Given that NF-kappaB and STAT3 are often activated coordinately during tumorigenesis, we examined whether STAT3 was activated by USP6 in our established cellular models of ABC and NF.

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We sought to dissect the mechanism by which USP6 activates STAT3.

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Given that NF-κB and STAT3 are often activated coordinately during tumorigenesis, we examined whether STAT3 was activated by USP6 in our established cellular models of ABC and NF.

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This validates our cellular model systems, and indicates that USP6 expression in human tumors triggers STAT3 and NF-kappaB signaling responses.

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Together, these results demonstrate that USP6 activates STAT3 exclusively through a Jak family kinase.

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Together, these results demonstrate that USP6 activates STAT3 exclusively through a Jak family kinase.

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USP6 activation of STAT3 occurs independently of NF-kappaB.
USP6 affects Wnt
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USP6 activates Wnt.
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USP6 activates Wnt. 6 / 6
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Additionally, the deubiquitinating enzymes UBPY and USP6 may promote the recycling of endocytosed FZD back to the surface and restore Wnt signaling.

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Interestingly, the Wnt antagonist Dickkopf-1 (DKK1) or LRP5/6 siRNA blocked USP6 induced Wnt signalling, suggesting that a Wnt-ligand receptor complex is required for USP6 function.
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A genomewide siRNA screen revealed that deubiquitinase USP6 overexpression could activate Wnt signaling by inhibition of Fzd7 endocytosis and its subsequent targeting for degradation [XREF_BIBR].

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In a separate whole-genome siRNA screen, USP6 was found to activate Wnt signalling by deubiquitylating Frizzled receptors and increasing their plasma membrane expression 28.

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USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds.

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USP6 enhances Wnt signaling by deubiquitylating Fzds, thereby increasing their cell-surface abundance.
USP6 decreases the amount of Wnt.
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USP6 decreases the amount of Wnt. 1 / 1
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USP6 was a target of miR-130a and the overexpression of miR-130a or inhibition of USP6 in UM MUM-2B and MUM-2C cell lines inhibited the expression of Wnt, β-catenin, and EGFR, and activated SMAD4 expression, while reducing UM cell migration and invasion abilities in vitro.
USP6 affects Neoplasms
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Lu et al. [6] reported a novel CTNNB1-USP6 fusion in IVF, showing that IVF is a USP6-induced neoplasm and should be included in USP6-rearranged lesions.The most common clinical presentation is a painless, slowly growing mass.

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Intra-articular nodular fasciitis and aneurysmal bone cyst seem to belong to the same biological spectrum defined as USP6-induced tumors according to the report [8].

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The findings of this case suggest that these two tumors reside in the same biologic spectrum defined as USP6-induced tumors.

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Although the molecular diagnosis was not performed, the findings of present case suggest that these two tumors reside in the same biologic spectrum defined as USP6-induced tumors.

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USP6-induced neoplasms are almost universally benign and cured by local excision.

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Recently, Oliveira and Chou suggested that aneurismal bone cysts and nodular fasciitis reside in the same biologic spectrum as USP6-induced tumors [9].
USP6 affects JAK1
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USP6 activates JAK1.
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USP6 activates JAK1. 3 / 3
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Jak1 in this clone was reduced to levels approximating those in control NIH3T3 cells (XREF_SUPPLEMENTARY), demonstrating that upregulation of Jak1 by USP6 is required for full activation of STAT3 by USP6.

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Jak1 is upregulated by USP6 in a USP dependent manner.

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Together, this group of experiments indicates that upregulation of Jak1 by USP6 is required not only for the production of autocrine and paracrine factors, but also for heightened STAT3 activation in response to them.
USP6 increases the amount of JAK1.
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USP6 increases the amount of JAK1. 2 / 2
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Our data support a model in which Jak1 levels are increased through de-ubiquitination by USP6, rendering cells hyper-sensitive to low levels of Jak1 agonists present in the microenvironment.

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RT-qPCR revealed that Jak1 mRNA levels were not increased by USP6 (XREF_SUPPLEMENTARY).
USP6 affects MMP9
1 | 1 3
USP6 increases the amount of MMP9.
1 | 3
USP6 increases the amount of MMP9. 3 / 3
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Especially, USP6 induces the transcription of MMP9 through activation of NF-kappaB.

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XREF_BIBR USP6 is sufficient to induce the expression of MMP9 and MMP10.

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XREF_BIBR, XREF_BIBR USP6 was shown to induce transcription of MMP9 through the activation of nuclear factor-kappaB (NF-kappaB) in a USP dependent manner.
Transcriptionally active USP6 increases the amount of MMP9. 1 / 1
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In this study we show that tre17 is sufficient to induce expression of mmp-9 and mmp-10, in a manner requiring its usp activity, but not its ability to bind arf6. Tre17 induces transcription of mmp-9 through activation of nuclear factor-kappab (nf-kappab), mediated in part by the gtpase rhoa and its effector kinase, rock.
USP6 activates MMP9.
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USP6 activates MMP9. 1 / 1
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Loss of the NFκB-binding site abrogated activation of the MMP-9 promoter by TRE17(long) in hFOB1.19 and HeLa ( xref ), indicating that NFκB is the key mediator of TRE17-induced MMP-9 gene transcription.

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Loss of either Hrp1 or Hrp3 leads to increased cryptic transcription, similar to that observed upon loss of Isw1 and Chd1 in budding yeast [XREF_BIBR - XREF_BIBR].

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Hrp1 forms the B component of the CFI polyadenylation factor and, when overexpressed, increases recognition of a weakened polyadenylation site and suppresses the defective transcription termination.

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TRalpha1/T3 via interacting with TRE1 mediated suppression of the transcription whereas TRalpha1/T3 via interacting with TRE2 activated transcription.

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TRα1/T3 via interacting with TRE1 mediated suppression of the transcription whereas TRα1/T3 via interacting with TRE2 activated transcription.
USP6 affects Interferon
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Not only does USP6 independently induce activation of the IFN signaling mediators JAK1 and STAT1, but it also renders ES cells exquisitely responsive to exogenous IFNs, potentiating activation of STAT1 and STAT3.

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USP6 synergistically enhanced chemokine production in response to exogenous IFN by inducing surface upregulation of IFNAR1 and IFNGR1.

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Single gene complementation of two Cluster V mutants, Tn : : Rv0712 and Tn : : hrp1 (hypoxic response protein 1, Rv2626c), restored the type I IFN response (XREF_FIG), suggesting that each of these genes is required for induction of type I IFNs.
USP6 affects PLA1A
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USP6 activates PLA1A. 2 / 2
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Thus, Hrp1p and Nab4p specifically interacts with the DSE from PGK1, and this interaction requires the presence of the sequence motifs.We asked whether the inability of hrp1 strains to promote NMD was[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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In this study, we have demonstrated that the RNA binding protein Hrp1 and Nab4 modulates the activity of the NMD pathway in yeast.

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As an independent prognostic factor, USP6 promotes the invasion and metastasis of colon cancer.

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Furthermore, cell function assay demonstrated that USP6 could promote colon cancer cells ' invasion invitro and liver metastasis invivo.

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As an independent prognostic factor, USP6 promotes the invasion and metastasis of colon cancer.

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Furthermore, cell function assay demonstrated that USP6 could promote colon cancer cells ' invasion invitro and liver metastasis invivo.
USP6 affects Histone_H3
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We show that, in addition to centromeric regions, a low level of CENP-A (Cnp1) associates with gene promoters where histone H3 is depleted by the activity of the Hrp1 (Chd1) chromatin remodeling factor.

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It is perhaps less surprising that the strong increase in H3 occupancy does not restrict chromatin accessibility since previous studies in fission yeast revealed that hrp1 and hrp3 deletions increase promoter H3 occupancy but do not affect MNase sensitivity of promoter regions [XREF_BIBR, XREF_BIBR].
USP6 affects DOT1L
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USP6 activates DOT1L. 2 / 2
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To determine whether TRE1 and TRE2 can mediate the transcriptional regulation of the Dot1L gene by T3 in vivo, we used a reconstituted Xenopus laevis oocyte transcription system, which allows the analysis of the promoter in the context of chromatin in vivo [XREF_BIBR].

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Thus, TRE2 likely mediates the induction of Dot1L by T3 in different organs during metamorphosis.
USP6 affects ARF6
1 | 1
USP6 activates ARF6. 2 / 2
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USP6 interacts with Arf6 through its N-terminus Tre2/Bub2/Csc16 (TBC) domain, and depletion of USP6 decreases Arf6 activity [19].
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Here we show that tre17 (also called tre-2 and usp6), a founding member of the tbc family, targets the arf family gtpase arf6, which regulates plasma membrane-endosome trafficking. Surprisingly, tre17 does not function as a gap for arf6 but rather promotes its activation in vivo. Forced expression of tre17 promotes the localization of arf6 to the plasma membrane, leading to arf6 activation, presumably due to facilitated access to membrane-associated guanine nucleotide exchange factors (gefs).
USP6 affects SMAD4
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USP6 increases the amount of SMAD4.
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USP6 increases the amount of SMAD4. 1 / 1
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USP6 was a target of miR-130a and the overexpression of miR-130a or inhibition of USP6 in UM MUM-2B and MUM-2C cell lines inhibited the expression of Wnt, β-catenin, and EGFR, and activated SMAD4 expression, while reducing UM cell migration and invasion abilities in vitro.
USP6 decreases the amount of SMAD4.
| 1
USP6 decreases the amount of SMAD4. 1 / 1
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USP6 was a target of miR-130a and the overexpression of miR-130a or inhibition of USP6 in UM MUM-2B and MUM-2C cell lines inhibited the expression of Wnt, β-catenin, and EGFR, and activated SMAD4 expression, while reducing UM cell migration and invasion abilities in vitro.
USP6 affects MMP10
1 | 1
Transcriptionally active USP6 increases the amount of MMP10. 1 / 1
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In this study we show that tre17 is sufficient to induce expression of mmp-9 and mmp-10, in a manner requiring its usp activity, but not its ability to bind arf6. Tre17 induces transcription of mmp-9 through activation of nuclear factor-kappab (nf-kappab), mediated in part by the gtpase rhoa and its effector kinase, rock.
USP6 increases the amount of MMP10. 1 / 1
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XREF_BIBR USP6 is sufficient to induce the expression of MMP9 and MMP10.
USP6 affects LRP6
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USP6 increases the amount of LRP6.
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USP6 increases the amount of LRP6. 1 / 1
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USP6 has also been shown to regulate cell surface abundance of LRP6 as expression of wild-type USP6 increases surface levels of LRP6.
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USP6 activates LRP6.
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USP6 activates LRP6. 1 / 1
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Contrary to RNF43, ubiquitin specific protease 6 (USP6) is a deubiquitylase; ectopic expression of USP6 increases cell surface abundance of Fzds and Lrp6 and activates beta-catenin pathway in tumor cells XREF_BIBR.
USP6 affects HEL
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USP6 bound to NAB2 inhibits HEL. 1 / 1
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These experiments reveal that these interactions do not depend on the presence of RNA, as interactions between Caf1 and Hrp1 or Caf1 and Nab2 were not reduced following RNase treatment (XREF_FIG and data not shown).
USP6 bound to CNOT7 inhibits HEL. 1 / 1
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These experiments reveal that these interactions do not depend on the presence of RNA, as interactions between Caf1 and Hrp1 or Caf1 and Nab2 were not reduced following RNase treatment (XREF_FIG and data not shown).
USP6 affects GRIN1
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USP6 inhibits GRIN1.
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USP6 inhibits GRIN1. 1 / 1
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USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells.
USP6 increases the amount of GRIN1.
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USP6 increases the amount of GRIN1. 1 / 1
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USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells.
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USP6 inhibits Cell Survival.
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Depletion of USP6 decreased cell survival specifically following high-LET alpha-particles and protons, but not by low-LET protons or x-rays.
USP6 activates Cell Survival.
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Jak1 is required for STAT3 activation by USP6, and both are required for USP6 mediated cell survival and tumorigenesis.
USP6 affects CTNNB1
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USP6 decreases the amount of CTNNB1.
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USP6 decreases the amount of CTNNB1. 1 / 1
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USP6 was a target of miR-130a and the overexpression of miR-130a or inhibition of USP6 in UM MUM-2B and MUM-2C cell lines inhibited the expression of Wnt, β-catenin, and EGFR, and activated SMAD4 expression, while reducing UM cell migration and invasion abilities in vitro.
USP6 activates CTNNB1.
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USP6 activates CTNNB1. 1 / 1
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Contrary to RNF43, ubiquitin specific protease 6 (USP6) is a deubiquitylase; ectopic expression of USP6 increases cell surface abundance of Fzds and Lrp6 and activates beta-catenin pathway in tumor cells XREF_BIBR.
TGFB affects USP6
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TGFB inhibits USP6.
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TGFB inhibits USP6. 1 / 1
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MTT proliferation assays revealed that each TGFB isoform decreased HRP-1 cell growth in a dose dependent manner, whereas RCHO-1 cells were resistant to the growth-suppressive effect of TGFB1 and TGFB3.
TGFB activates USP6.
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TGFB activates USP6. 1 / 1
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Activation of ERK, MAPK14 (p38 MAPK), or SMAD pathways is known to play a role in cell proliferation, and we found that TGFB activates these pathways in both HRP-1 and RCHO-1 cells in an isoform specific manner.
RAC1 affects USP6
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RAC1 increases the amount of USP6.
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GTP-bound active RAC1 increases the amount of USP6. 1 / 1
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Coexpression of activated alleles of Cdc42 or Rac1 also caused complete redistribution of TRE17 to the plasma membrane, where it partially colocalized with the GTPases in filopodia and ruffles, respectively.
RAC1 activates USP6.
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RAC1 activates USP6. 1 / 1
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In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.
JAK1 affects USP6
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JAK1 inhibits USP6.
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JAK1 inhibits USP6. 1 / 1
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Strikingly, both complete and partial depletion of Jak1 significantly reduced the mass of USP6 induced tumors (XREF_FIG).
JAK1 activates USP6.
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JAK1 activates USP6. 1 / 1
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Strikingly, we found that Jak1 levels were significantly increased in NIH3T3 and MC3T3 cell lines expressing USP6, in a dox dependent manner (XREF_FIG).
CDC42 affects USP6
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CDC42 increases the amount of USP6.
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GTP-bound active CDC42 increases the amount of USP6. 1 / 1
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Coexpression of activated alleles of Cdc42 or Rac1 also caused complete redistribution of TRE17 to the plasma membrane, where it partially colocalized with the GTPases in filopodia and ruffles, respectively.
CDC42 activates USP6.
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CDC42 activates USP6. 1 / 1
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In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.
Antirheumatic Agents increases the amount of USP6.
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Antirheumatic Agents increases the amount of USP6. 1 / 1
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ctd
No evidence text available
Antirheumatic Agents decreases the amount of USP6.
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Antirheumatic Agents decreases the amount of USP6. 1 / 1
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ctd
No evidence text available
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Valproic acid increases the amount of USP6. 1 / 1
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ctd
No evidence text available
Methylmercury chloride increases the amount of USP6. 1 / 1
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ctd
No evidence text available
Indometacin affects USP6
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Indometacin decreases the amount of USP6. 1 / 1
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ctd
No evidence text available
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Hsa-miR-423-5p decreases the amount of USP6. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-26b-5p decreases the amount of USP6. 1 / 1
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biopax:mirtarbase
No evidence text available
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Hsa-miR-10b-5p decreases the amount of USP6. 1 / 1
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biopax:mirtarbase
No evidence text available
Histamine affects USP6
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We then examined if histamine may enhance NGF promoter activity in keratinocytes.It is reported that human NGF gene contains two TREs, TRE1 (-62/-56 bp) and TRE2 (+35/+41 bp), and these may act as enh[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
Glucose affects USP6
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Glucose activates USP6. 1 / 1
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Conversely, glucose depletion enhanced only the formation of clear foci of Pab1-GFP, Pbp1-GFP, and Hrp1-GFP, but not Rpg1-GFP, Prt1-GFP, and Nip1-GFP in the cytoplasm.
Doxorubicin affects USP6
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Doxorubicin decreases the amount of USP6. 1 / 1
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ctd
No evidence text available
Dimethylarsinic acid increases the amount of USP6. 1 / 1
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ctd
No evidence text available
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Dexamethasone decreases the amount of USP6. 1 / 1
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ctd
No evidence text available
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Copper(II) sulfate increases the amount of USP6. 1 / 1
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ctd
No evidence text available
Butanal affects USP6
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Butanal decreases the amount of USP6. 1 / 1
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ctd
No evidence text available
Bisphenol A affects USP6
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Bisphenol A decreases the amount of USP6. 1 / 1
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ctd
No evidence text available
Wnt affects USP6
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Wnt activates USP6. 1 / 1
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Inhibition of Wnt signaling using Dickkopf-1 (DKK1) or a Porcupine (PORCN) inhibitor significantly decreased the growth of USP6 driven xenograft tumors, indicating that Wnt signaling is a key target of USP6 during tumorigenesis.
USP6 affects transport
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Two members of the tre-2 and USP6, BUB2, cdc16 (TBC1) domain family of proteins, Akt substrate of 160 kDa (also known as AS160 or TBC1D4) and TBC1D1, have been proposed as potential sites for the convergence of insulin and exercise signaling to stimulate glucose transport in skeletal muscle.

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In ABC, both neoplastic cells and other cells in the microenvironment exhibited P-STAT3 activation (XREF_FIG, left), suggesting that USP6 might induce paracrine signaling (as was confirmed below).

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For example, HRP1 and CLP1, both induced in response to MMS, are subunits of cleavage factor I, required for the cleavage and polyadenylation of 3 ' mRNA ends [XREF_BIBR].
USP6 affects glucose
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USP6 activates glucose. 1 / 1
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Two members of the tre-2 and USP6, BUB2, cdc16 (TBC1) domain family of proteins, Akt substrate of 160 kDa (also known as AS160 or TBC1D4) and TBC1D1, have been proposed as potential sites for the convergence of insulin and exercise signaling to stimulate glucose transport in skeletal muscle.

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In contrast, cohesin mutants rad21 and psc3 were rescued by loss of the RNA elimination pathway (Erh1, Mmi1, and Red1), and loader mutant mis4 was rescued by loss of Hrp1 mediated chromatin remodeling.

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Tre2 (USP6NL) promotes colorectal cancer cell proliferation via Wnt and beta-catenin pathway.
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USP6 and TRE17 was shown to induce cell migration in the TRE17-RhoA and ROCK or IKK-NF-kappaB-MMP-9 signaling pathway.
USP6 affects cell cycle
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USP6 depletion caused cell cycle arrest and a deficiency in CDD repair mediated through instability of poly (ADP-ribose) polymerase-1 (PARP-1) protein.
USP6 affects cas9
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USP6 activates cas9. 1 / 1
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Studies have used the TRE3G (Tet-On-3G) and TRE2 Tet-On promoters to activate Cas9 proteins in an animal model and human immortalised cell lines respectively under the control of administered doxycycline [ xref , xref ].
USP6 affects abacavir
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USP6 activates abacavir. 1 / 1
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It also illustrates the added value of genomic analyses in the setting of an ABC lesion : complex clonal aberrations argues for a lesion secondary to a malignant proliferation whereas USP6 rearrangement allows the diagnosis of primary ABC.
USP6 affects TNFSF10
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USP6 activates TNFSF10. 1 / 1
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Finally, apoptosis is mediated through the pro apoptotic ligand TRAIL, which is synergistically induced by Type I IFN and USP6.
USP6 affects RHOA
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USP6 activates RHOA. 1 / 1
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To determine whether RhoA was activated by TRE17, we performed pulldown assays using the Rho-binding domain (RBD) of Rhotekin (which binds to RhoA in a GTP-dependent manner) as an affinity reagent.
USP6 affects RAB
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USP6 activates RAB. 1 / 1
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The product of the human Tre2 oncogene is structurally related to the Ypt and Rab GTPase activating proteins (Ypt and Rab GAPs).
USP6 affects PARP1
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USP6 inhibits PARP1. 1 / 1
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USP6 was competent to induce Erk activation and prevent PARP cleavage upon serum starvation, and this effect was abrogated by depletion of Jak1 or STAT3 (XREF_FIG).
USP6 affects Osteosarcoma
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Overexpression of the Ubiquitin Specific Proteases USP43, USP41, USP27x and USP6 in Osteosarcoma Cell Lines: Inhibition of Osteosarcoma Tumor Growth and Lung Metastasis Development by the USP Antagonist PR619.
USP6 affects NFKB1
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USP6 activates NFKB1 bound to RELA. 1 / 1
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signor
These data confirm that tre17 activates nfkappab in a usp-dependent manner
USP6 affects IGFALS
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USP6 activates IGFALS. 1 / 1
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The aggregation of the human homologs of HRP-1, hnRNP-A1, and hnRNP-A3 was recently discovered to cause multisystem proteinopathy and ALS and FTLD.
USP6 affects IFNGR1
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USP6 activates IFNGR1. 1 / 1
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USP6 synergistically enhanced chemokine production in response to exogenous IFN by inducing surface upregulation of IFNAR1 and IFNGR1.
USP6 affects IFNAR1
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USP6 activates IFNAR1. 1 / 1
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USP6 synergistically enhanced chemokine production in response to exogenous IFN by inducing surface upregulation of IFNAR1 and IFNGR1.
USP6 affects HIRA
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USP6 inhibits HIRA. 1 / 1
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XREF_BIBR At the hrp1 + locus loss of HIRA function resulted in marked changes to the MNase profile which extended throughout the entire gene and into the neighboring genes (atg12 + and pap1 +) (XREF_FIG; Fig.
USP6 affects Glu-Ser
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USP6 inhibits Glu-Ser. 1 / 1
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USP6 inhibited ES xenograft growth in nude but not NSG mice and was accompanied by increased intra-tumoral chemokine production and infiltration and activation of NK cells, dendritic cells, and macrophages, consistent with a requirement for innate immune cells in mediating the anti-tumorigenic effects of USP6.
USP6 affects GREM1
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Modified USP6 activates GREM1. 1 / 1
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In particular, USP6 overexpression inhibits the expression of bone morphogenetic protein BMP4, a key regulator of osteogenesis, and simultaneously augments expression the BMP antagonist Gremlin-1 [53][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP6 affects GATA1
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USP6 increases the amount of GATA1. 1 / 1
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These results indicate that TRE2, via T3-TRalpha1, mediates the positive regulation of the Gata1 gene transcription.
USP6 affects ERK
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USP6 activates ERK. 1 / 1
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USP6 was competent to induce Erk activation and prevent PARP cleavage upon serum starvation, and this effect was abrogated by depletion of Jak1 or STAT3 (XREF_FIG).
USP6 affects EGFR
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USP6 decreases the amount of EGFR. 1 / 1
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USP6 was a target of miR-130a and the overexpression of miR-130a or inhibition of USP6 in UM MUM-2B and MUM-2C cell lines inhibited the expression of Wnt, β-catenin, and EGFR, and activated SMAD4 expression, while reducing UM cell migration and invasion abilities in vitro.
USP6 affects Cohesin
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USP6 inhibits mutated Cohesin. 1 / 1
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In contrast, cohesin mutants rad21 and psc3 were rescued by loss of the RNA elimination pathway (Erh1, Mmi1, and Red1), and loader mutant mis4 was rescued by loss of Hrp1 mediated chromatin remodeling.
USP6 affects Chemokine
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eidos
USP6 synergistically enhanced chemokine production in response to exogenous IFN by inducing surface upregulation of IFNAR1 and IFNGR1 .
USP6 affects CENPA
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USP6 activates CENPA. 1 / 1
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The CHD remodeling factor Hrp1 stimulates CENP-A loading to centromeres.
USP6 affects BMP4
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Modified USP6 decreases the amount of BMP4. 1 / 1
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In particular, USP6 overexpression inhibits the expression of bone morphogenetic protein BMP4, a key regulator of osteogenesis, and simultaneously augments expression the BMP antagonist Gremlin-1 [53][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP6 affects BMP
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Modified USP6 activates BMP. 1 / 1
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In particular, USP6 overexpression inhibits the expression of bone morphogenetic protein BMP4, a key regulator of osteogenesis, and simultaneously augments expression the BMP antagonist Gremlin-1 [53][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP6 affects Aneuploidy
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Active USP6 inhibits Aneuploidy. 1 / 1
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bel
Similarly, the inactivation of the evolutionarily related DUB in yeast, Ubp6, increases the cellular fitness of aneuploid cells, which have been shown to incur increased proteotoxic stresses due to chromosomal imbalance [66].

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As many as 69% of primary ABCs demonstrate a characteristic clonal t(16;17) genetic translocation which can lead to an upregulation of the TRE17/USP6 oncogene [4].
TGFB3 affects USP6
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TGFB3 inhibits USP6. 1 / 1
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MTT proliferation assays revealed that ERK pathway is partially implicated in TGFB3 reduced HRP-1 cell proliferation.
Smoke affects USP6
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Smoke increases the amount of USP6. 1 / 1
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ctd
No evidence text available
STAT3 affects USP6
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STAT3 activates USP6. 1 / 1
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To test this, we examined STAT3 activation in USP6 and NIH3T3 cells in which NF-kappaB was inhibited through expression of IkappaB-alpha super repressor.
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Plant Extracts increases the amount of USP6. 1 / 1
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No evidence text available
HSPB3 affects USP6
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HSPB3 activates USP6. 1 / 1
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Previously, we demonstrated that silencing of cyclic AMP (cAMP) response element binding protein 3 like 1 (CREB3L1), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication.
EGF affects USP6
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EGF increases the amount of USP6. 1 / 1
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bel
Furthermore, the subcellular localization of TRE17 was dramatically regulated by these GTPases and mitogens. Under serum-starved conditions, TRE17 localized predominantly to filamentous structures within the cell. Epidermal growth factor (EGF) induced relocalization of TRE17 to the plasma membrane in a Cdc42-/Rac1-dependent manner.
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No evidence text available
4,4'-sulfonyldiphenol decreases the amount of USP6. 1 / 1
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No evidence text available

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That is, TR also bound predominantly to the TRE2 in the tail of premetamorphic tadpoles treated with or without T3 for 2days.