IndraLab

Statements

USP9X affects MCL1

1 | 26

USP9X deubiquitinates MCL1. 10 / 26

1 | 25

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"Conversely, the deubiquitinase USP9X reverses polyubiquitination of Mcl-1 and promotes its stability [XREF_BIBR]."

22125448

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"USP9X can deubiquitinate and stabilize MCL1, a protein essential for the survival of stem and progenitor cells from multiple lineages, thereby promoting cell survival."

30319415

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"The inhibition of USP9x should increase the ubiquitination of Mcl-1."

26542215

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"USP9X deubiquitinates and stabilizes MCL-1, a pro survival BCL2 family member XREF_BIBR, whose overexpression is associated with several neoplastic conditions XREF_BIBR - XREF_BIBR."

21283576

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"USP9X interacts with and deubiquitinates MCL-1, thereby stabilising it."

34079080

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"Deubiquitination of Mcl-1 by USP9X."

24814761

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"USP9X also deubiquitinated Mcl-1 in vitro, and generated free mono-ubiquitin [XREF_BIBR]."

24814761

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"XREF_BIBR, XREF_BIBR, XREF_BIBR In addition, a recent study showed that de-ubiquitinase USP9X inhibits Mcl-1 ubiquitination, thereby stabilizing protein levels and promoting tumor cell survival."

22552282

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"Studies have shown that USP9X regulates protein transport, cell migration, and cell adhesion by deubiquitinating NUAK1, MARCH, MCL-1, mTOR, SMN, Bcl 10, and PEX5 to participate in crucial pathophysiol[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

32442538

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"Previous studies showed that USP9X deubiquitinates MCL1 and promotes cancer cell survival in human follicular lymphomas and diffuse large B cell lymphomas 19."

29449692

USP9X leads to the deubiquitination of MCL1-K40Q. 1 / 1

| 1

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"Given that USP9X inhibition by WP1130 restored poly-ubiquitination of acetylation-mimetic K40Q MCL1 (Figure 4C) and effectively reduced its protein abundance (Figures 4F and 4G), we next evaluated MCL1 levels in breast and prostate cancer cells treated with WP1130."

34758305

USP9X affects SMAD4

1 | 21

USP9X deubiquitinates SMAD4. 10 / 18

1 | 17

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"Subsequently it was shown that USP9X deubiquitylates SMAD4 that is monoubiquitylated at K519 (XREF_FIG)."

25007997

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"This inhibitory event is readily reversed by FAM and USP9x, which deubiquitinates Smad4 and restores its responsiveness to TGF-beta [XREF_BIBR]."

20940046

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"FAM and USP9X is required for TGFbeta induced migration of MDA-MB-231 breast cancer cells; mechanistically, FAM and USP9X inhibits the monoubiquitination of SMAD4, a modification that blocks the association of SMAD4 with phospho-SMAD2 [XREF_BIBR] (XREF_FIG)."

27844253

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"Usp9x deubiquitylation of Smad4 is essential for signalling by members of the Tgf-beta family XREF_BIBR, XREF_BIBR."

23861879

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"USP9X (also known as FAM) deubiquitylates SMAD4 and thereby sustains TGF-beta signaling (Dupont etal."

26085183

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"The ubiquitin ligase Ectodermin/TIF1γ promotes, while the deubiquitinases USP9X and USP4 antagonize SMAD4 monoubiquitination [28,85,86]."

35682605

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"For example USP9X may upregulate ID2 gene expression by deubiquitinating and stabilizing the transcription factor SMAD4 (Dupont et al., 2009)."

21925315

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"USP9X reverses Smad4 ubiquitination to reactivate the pathway and reinstate TGFbeta signaling."

25606592

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"The deubiquitination of Smad4 by FAM is direct."

19135894

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"Dupont et al. (2009) now demonstrate that FAM deubiquitinates Smad4 that has been monoubiquitinated by Ecto/TIF1γ."

19135880

Modified USP9X leads to the deubiquitination of SMAD4. 3 / 3

| 3

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"Strikingly, overexpression of wild-type FAM, but not of the catalytically inactive FAM mutant, inhibited Smad4 monoubiquitination in vivo."

19135894

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"Loss of USP9X therefore prevents deubiquitination of SMAD4, enhancing tumour progression."

24292195

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"Overexpression of FAM also inhibits monoubiquitination of endogenous Smad4."

19135894

USP9X deubiquitinates ubiquitinated SMAD4. 1 / 1

| 1

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"FAM and Usp9x deubiquitinates the monoubiquitinated SMAD4 (which is exported from the nucleus (XREF_FIG)) and thereby enables SMAD2 and SMAD4 complex formation."

25317929

USP9X affects YAP1

1 | 14

USP9X deubiquitinates YAP1. 10 / 15

1 | 14

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"YAP1 is deubiquitinated and stabilized by USP9X, thereby promoting breast cancer cell survival and resulting in chemotherapy resistance (47)."

37920433

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"A previous study demonstrated that deubiquitinase USP9X could interact with and deubiquitinate YAP, and then enhanced its protein stability.25 Interestingly, the results of RNA pull-down followed by mass spectrometry analysis demonstrated that USP9X potentially associated with LINC01433."

31632054

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"Mechanistically, it was found that hsa_circ_0024093 could regulate the expression of USP9X, which further induced YAP1 deubiquitination to stabilize YAP1 protein."

34631281

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"Conversely, the deubiquitinating enzyme (DUB) ubiquitin specific peptidase 9 X-linked (USP9X) deubiquitinates and stabilizes YAP1, thereby promoting breast cancer cell survival and chemotherapy resist[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38537774

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"It has been previously reported that the deubiquitination enzyme USP9X deubiquitinates and stabilizes YAP in breast cancer cells, thus promoting cancer cell survival [13]."

37349820

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"In addition, it has been shown that USP9X induces YAP1 deubiquitination to enhance cell proliferation and metastasis in breast carcinoma.18 Thus, we further speculated whether hsa_circ_0024093 could affect USP9X to promote YAP1 deubiquitination and stabilize YAP1 protein."

34631281

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"USP9X induces YAP1 deubiquitination to stabilize YAP1."

34631281

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"Mechanistically, USP9X deubiquitinates and stabilizes YAP1."

29449692

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"Furthermore, the ubiquitination of YAP1 was reduced by USP9X upregulation in VSMCs and increased by USP9X knockdown in PDGF-BB-treated VSMCs (Figures S4E and S4F)."

34631281

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"Here we demonstrate that the deubiquitination enzyme USP9X deubiquitinates and stabilizes YAP1, thereby promoting cancer cell survival."

29449692

USP9X affects CD274

1 | 9

USP9X deubiquitinates CD274. 8 / 9

1 | 8

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"Mechanistically, they found that USP9X deubiquitinated PD-L1 and stabilized its protein expression, thereby promoting immune escape of tumor cells in OSCC using immunohistochemistry, immunoprecipitation, western blotting, liquid chromatography-mass spectrometry and a T-cell-mediated tumor cell killing assay.3."

40337608

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"Moreover, USP9X directly binds PD-L1, and USP9X reduces PD-L1 ubiquitination and increases its protein abundance."

37415977

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"Contrary, it is reported that PD-L1 can be deubiquitinated by CSN5, USP22, USP7, USP9X, and OTUB1 (Feng et al.)."

37822939

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"In oral squamous cell carcinoma (OSCC), USP9X deubiquitinates PD-L1 as well as maintain its protein stable expression [164]."

37658402

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"Indeed, USP9X induces PD-L1 deubiquitination and regulates its stabilization by ubiquitin specific protease activity."

32850399

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"Among them, USP9X, CSN5, USP22 and USP7 are responsible for the deubiquitination and stabilization of PD-L1 in tumor cells [98–101]."

36998063

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"Moreover, USP9X, USP8, and CSN5 can deubiquitinate PD-L1, and OTUB1 increase PD-L1 levels by preventing new synthetic PD-L1 from entering the ERAD."

38715050

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"Our data indicate that USP9X deubiquitinates and stabilizes PD-L1."

29992764

Modified USP9X leads to the deubiquitination of CD274. 1 / 1

| 1

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"In Oral Squamous Cell Carcinoma (OSCC) cells, the high expression of USP9X increases the deubiquitination of PD-L1 and reduces its degradation, resulting in protein accumulation in these cells."

32850399

USP9X affects NFE2L2

| 9

USP9X deubiquitinates NFE2L2. 9 / 9

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"Further researches revealed that USP9X could reduce the Nrf2 ubiquitination level in AGEs-treated GMCs, suggesting that USP9X, depending on its deubiquitinase activity, stabilized Nrf2 protein, and in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

32442538

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"These data suggested that USP9X, relying on its deubiquitinase activity, reduced Nrf2 ubiquitination level to increase its protein expression, promoting the activation of Nrf2-ARE pathway.DN is one of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

32442538

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"Considering that USP9X increased the protein expression of Nrf2 in model cells in a deubiquitinase activity-dependent manner, we supposed that USP9X might directly deubiquitinate Nrf2 to inhibit its d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

32442538

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"USP9X suppresses ferroptosis in diabetic kidney disease by deubiquitinating Nrf2 in vitro."

39967230

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"An interaction between USP9X and Nrf2 has been verified and USP9X deubiquitinated Nrf2."

39967230

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"USP9X deubiquitinated Nrf2 in HK-2 cells."

39967230

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"Furthermore, USP9X overexpression reduced polyubiquitination of Nrf2, revealing that USP9X deubiquitinated Nrf2 in HK-2 cells (Figure 2(K))."

39967230

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"Based on that Nrf2 ubiquitination is closely related to DN, and that USP9X can disrupt the ubiquitination and degradation process of substrate proteins which exert anti-OSS effects, we speculated that[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

32442538

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"However, USP9X overexpression after Nrf2 interference could not reverse the above changes induced by AGEs ( Fig. 6 ), suggesting that Nrf2 mediated the inhibitory effects of USP9X on fibrosis developm[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

32442538

USP9X affects ERG

1 | 7

USP9X deubiquitinates ERG. 7 / 8

1 | 7

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"Previously, we found that ERG undergoes ubiquitination and then is deubiquitinated by USP9X in prostate cancer cells to prevent its proteasomal degradation."

27626314

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"We found that ERG stability is maintained by the deubiquitinase USP9X and demonstrated that a small molecule inhibitor (WP1130) of USP9X could effectively block ERG deubiquitination resulting in rapid[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

36330954

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"Indeed, previous reports have shown Usp9x deubiquitinates and stabilizes ERG, and our previously described DUB inhibitor (WP1130) demonstrated anti-tumour efficacy in ERG driven prostate cancer XREF_BIBR."

28198367

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"Wang et al. demonstrated that ubiquitin specific peptidase 9, X linked (USP9X), a deubiquitinase enzyme, binds ERG in VCaP prostate cancer cells expressing TMPRSS2-ERG and deubiquitinates ERG in vitro XREF_BIBR."

27208692

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"USP9X binds to the ETS domain in ERG protein; therefore, USP9X deubiquitinates and stabilizes full-length ERG and TMPRSS2 - ERG fusion gene products."

30217566

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"A role for ERG ubiquitination in prostate cancer cells was also demonstrated by Wang et al. who showed that the enzyme USP9X, which is highly expressed in ERG positive prostate tumours, mediates ERG deubiquitination and thus its stabilization XREF_BIBR."

27208692

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"Here, we show that ubiquitin specific peptidase 9, X linked (USP9X), a deubiquitinase enzyme, binds ERG in VCaP prostate cancer cells expressing TMPRSS2-ERG and deubiquitinates ERG in vitro."

24591637

USP9X affects SNCA

1 | 6

USP9X deubiquitinates SNCA. 6 / 7

1 | 6

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"USP9X Deubiquitinates Mono-Ubiquitinated alpha-Synuclein."

36831318

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"In the brain tissues of PD patients, USP9X colocalises with alpha-synuclein inclusions, and in vitro studies show a functional interaction; whilst monoubiquitylated alpha-synuclein is degraded by the proteasome, USP9X deubiquitylation of alpha-synuclein directs its degradation by the less efficient autophagy pathway [XREF_BIBR]."

25672900

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"We recently found that USP9X deubiquitinates alpha-synuclein, and that this process determines the partition of alpha-synuclein between the proteasomal and autophagy pathways."

22361583

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"Usp9x also deubiquitylates mono-ubiquitylated alpha-synuclein raising the possibility it may play a role in the progression of neurodegenerative diseases such as Parkinson 's disease XREF_BIBR."

23861879

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"Moreover, USP9X can increase MAPT phosphorylation via a second mechanism, by deubiquitinating the protein alpha-synuclein (SNCA) [XREF_BIBR], which functions as a connecting mediator between the glycogen synthase kinase 3beta (GSK3B) and MAPT and has been shown to stimulate MAPT phosphorylation via GSK3B in vitro [XREF_BIBR]."

27878758

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"We now report that the deubiquitinase USP9X interacts in vivo with and deubiquitinates alpha-synuclein."

22065755

USP9X affects IRS2

1 | 6

USP9X deubiquitinates IRS2. 6 / 7

1 | 6

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"In addition, USP9X in LNCaP cells was not co-immunoprecipitated with IRS-2 (XREF_SUPPLEMENTARY), suggesting that USP9X does not deubiquitinate IRS-2 in LNCaP cells."

30338032

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"Knockdown of USP9X dramatically reduced IRS-2 protein level, increased IRS-2 ubiquitination, and promoted the proteasomal degradation of IRS-2 in PC3 cells, suggesting that USP9X also deubiquitinates IRS-2 to prevent its proteasomal degradation."

30338032

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"Thus, it is possible that USP9X preferentially deubiquitinates IRS-2 much more than IRS-1 because of the difference of such ubiquitination patterns."

30338032

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"In addition, the interaction between USP9X and IRS-2 was not observed in LNCaP cells (XREF_SUPPLEMENTARY), suggesting that USP9X in LNCaP does not deubiquitinate and stabilize IRS-2 because of the absence of interaction between them."

30338032

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"IRS-2 deubiquitination by USP9X maintains anchorage independent cell growth via Erk1/2 activation in prostate carcinoma cell line."

30338032

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"These data suggest that USP9X deubiquitinates IRS-2 and prevents its proteasomal degradation."

30338032

USP9X affects EPS15

1 1 | 5

USP9X deubiquitinates EPS15. 5 / 7

1 1 | 5

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"USP9X Controls EGFR Fate by Deubiquitinating the Endocytic Adaptor Eps15."

38113830

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"USP9X has been reported to simultaneously regulate endocytosis of the EGFR by deubiquitinating its endocytic adaptor Eps15 and ubiquitin ligase Itch in tumor cell lines (17, 18, 40)."

35389885

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"Interestingly, recent findings further demonstrate that EPS15 de-ubiquitination by USP9X affects EGFR internalization and its trafficking to lysosomes."

27008177

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"These include USP9x, which deubiquitylates EPS15 to relieve its autoinhibition and thereby promotes trafficking and downregulation of ubiquitylated receptors (Savio et al., 2016) (Fig. 1B)."

36825571

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"USP9X has been shown to regulate EGFR endocytosis in tumor cell lines by deubiquitinating its endocytic adaptor Eps15 and ubiquitin ligase Itch [31]."

36653359

USP9X affects CTNNB1

1 | 1 5

USP9X deubiquitinates CTNNB1. 6 / 7

1 | 1 5

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"In the Wnt pathway, FAM deubiquitinates betacatenin, preventing its degradation in mammalian cells, but the effect of FAM activity on Wnt signaling was not noted."

18797952

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"A growing number of substrate-specific mammalian DUBs involved in tumorigenesis are continually being revealed such as USP1 and USP9X, which deubiquitinate FANCD2 and β-catenin, respectively ( Nijman [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

16455486

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"Deubiquitinase USP9X deubiquitinates beta-catenin and promotes high grade glioma cell growth."

27783990

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"As shown in Figure XREF_FIG, knockdown of USP9X increased the ubiquitination of beta-catenin and subsequent degradation."

27783990

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"Deubiquitinase USP9X deubiquitinates beta-catenin and promotes high grade glioma cell growth."

32364424

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"Deubiquitinase USP9X deubiquitinates β-catenin and promotes high grade glioma cell growth."

27783990

USP9X affects ZBTB38

1 | 5

USP9X deubiquitinates ZBTB38. 5 / 6

1 | 5

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"USP9X deubiquitinates ZBTB38."

29490077

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"It has been reported that USP9X can deubiquitinate and stabilize ASK1 and ZBTB38 and therefore, antagonize the OSS damage [ 14 , 15 ]."

32442538

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"We thus conclude that USP9X activity triggers the deubiquitination of ZBTB38 in cells."

29490077

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"By poly-ubiquitination assays, we observed that USP9X causes deubiquitination of ZBTB38, even in cells over-expressing RBBP6 and conversely that inactivation of USP9X amplifies the polyubiquitination induced by RBBP6 over-expression (XREF_SUPPLEMENTARY)."

29490077

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"Together these data show that USP9X deubiquitinates ZBTB38, both in basal conditions, and in conditions where ZBTB38 ubiquitination is augmented by RBBP6."

29490077

USP9X affects TOP3B

| 6

USP9X deubiquitinates TOP3B. 6 / 6

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"Inactivation of USP9X destabilizes TOP3B, and depletion of both TDRD3 and USP9X does not promote further TOP3B ubiquitylation."

37980342

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"We also find that USP9X antagonizes TOP3B ubiquitylation by the E3 ligase Mind bomb E3 Ubiquitin Protein Ligase 1 (MIB1)."

37980342

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"These results indicate that USP9X deubiquitylates TOP3B only when bound to TDRD3."

37980342

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"To confirm the role of TDRD3 in mediating TOP3B deubiquitylation by USP9X, we depleted USP9X in TDRD3KO HCT116 cells."

37980342

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"This result confirms that the DUB activity of USP9X is responsible for the stabilization of TOP3B and TDRD3.Altogether, we conclude that USP9X deubiquitylates and stabilizes TOP3B and that TDRD3 acts by mediating the deubiquitylation of TOP3B by USP9X."

37980342

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"Although it has been reported that USP9X interacts with, deubiquitylates, and stabilizes TDRD3 and that USP9X is stimulated by TDRD3 , our study reveals that TOP3B is a substrate of USP9X and establishes that USP9X requires TDRD3 to deubiquitylate TOP3B."

37980342

USP9X affects NUDT1

| 6

USP9X deubiquitinates NUDT1. 6 / 6

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"Co-IP data show that USP9X interacts with and deubiquitinates MTH1."

39075342

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"USP9X deubiquitinates MTH1 in HGC-27 cells."

39075342

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"We observed that overexpression of wildtype USP9X significantly reduced the ubiquitination of MTH1, while mutant USP9X had the opposite function (Fig. 3A)."

39075342

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"Conversely, knockdown of USP9X greatly upregulated MTH1 ubiquitination (Fig. 3B)."

39075342

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"Our observations that USP9X interacts with and deubiquitinates MTH1 in HGC-27 cells and controls the proliferation, survival, migration, and invasion of GC cells expand our knowledge about the function and target of USP9X in cancer biology."

39075342

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"In summary, our study reveals that USP9X can control the proliferation, survival, migration and invasion of GC cells by interacting with and deubiquitinating MTH1."

39075342

USP9X affects AMOT

| 6

USP9X deubiquitinates AMOT. 3 / 3

| 3

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"Thus, it appears that the direct effect of limiting deubiquitylation of AMOT by USP9x offsets the reduced potential for ubiquitylation due to lower E3 ligase levels."

27462448

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"USP9X in the DUBs (ubiquitin-specific protease family) could bind to and deubiquitinate AMOT."

34539895

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"USP9X also ameliorates the oncogenic activity of transcriptional coactivator YAP and tafazzin, which are core components of the Hippo pathway, by deubiquitinating their inhibitor, angiomotin (10)."

31002345

USP9X deubiquitinates AMOT on K496. 2 / 2

| 2

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"USP9X leads to deubiquitinate AMOT at Lys 496, resulting in stabilization of AMOT and reduced YAP and TAZ activity."

29366444

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"USP9x acts to deubiquitylate Angiomotin at lysine 496, resulting in stabilization of Angiomotin and lower YAP and TAZ activity."

27462448

Modified USP9X leads to the deubiquitination of AMOT. 1 / 1

| 1

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"We demonstrate that loss of USP9x leads to increased ubiquitylation of AMOT, resulting in reduced AMOT levels."

27462448

USP9X affects XIAP

| 5

USP9X deubiquitinates XIAP. 4 / 4

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"We reasoned that USP9X deubiquitylates XIAP to regulate mitotic survival."

27317434

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"These studies revealed a mitosis specific function for the ubiquitin specific protease 9X (USP9X), which we show to deubiquitylate and stabilize XIAP in order to promote mitotic survival."

27317434

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"69 USP9X also can induce deubiquitylation and stabilization of XIAP, resulting in increased resistance toward MTAs in aggressive B‐cell lymphoma."

36967563

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"Engel et al. [XREF_BIBR] demonstrate that USP9X is the mitotic deubiquitinase of the X linked inhibitor of apoptosis protein (XIAP) and that deubiquitylation and stabilization of XIAP by USP9X lead to increased resistance toward mitotic spindle poisons."

27766120

Modified USP9X leads to the deubiquitination of XIAP. 1 / 1

| 1

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"Indeed, ubiquitylation of XIAP was substantially increased upon silencing or chemical inhibition of USP9X (Figs XREF_FIG E and XREF_FIG A) in mitotic cells, while forced expression of USP9X attenuated XIAP ubiquitylation (Fig XREF_FIG A)."

27317434

USP9X affects TDRD3

| 5

USP9X deubiquitinates TDRD3. 5 / 5

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"USP9X prevents TDRD3 ubiquitination."

28101374

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"To test whether USP9X de-ubiquitinates TDRD3 in cells, we transfected HeLa cells with either control or USP9X specific siRNA, and measured TDRD3 ubiquitination."

28101374

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"USP9X prevents polyubiquitination of TDRD3 in cells."

28101374

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"We observed that when the cellular levels of USP9X were reduced by siRNA, the TDRD3 ubiquitination levels markedly increased (XREF_FIG, upper panel -- compare lane 2 to lane 5) and inhibition of the proteasome greatly augmented this difference (XREF_FIG, upper panel -- compare lane 3 to lane 6), suggesting that USP9X is necessary to suppress TDRD3 ubiquitination."

28101374

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"The interaction between TDRD3 and the ubiquitin-specific peptidase 9 X-linked (USP9X), which is dependent on arginine methylation of USP9X, prevents TDRD3 ubiquitination, together with a significant i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

33753223

USP9X affects SMURF1

1 | 4

USP9X deubiquitinates SMURF1. 4 / 5

1 | 4

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"Moreover, USP9X deubiquitinates and stabilizes SMURF1, a member of the NEDD4 family of ubiquitin ligases; silencing USP9X expression in MDA-MB-231 breast cancer cells destabilized SMURF1 and inhibited SMURF1 dependent cell migration [XREF_BIBR]."

27844253

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"In another study, in breast cancer cells ubiquitination of Smurf1 could be reversed by the deubiquitinating enzyme USP9X through Smurf1 WW domain binding, which improved Smurf1 's stability."

33718111

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"USP9X (FAM) deubiquitylates the autoubiquitylated E3 ligases Itch and SMURF1 and, thereby, increases their stability XREF_BIBR - XREF_BIBR."

24714733

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"However, Xie et al. found that USP9X can deubiquitinate and stabilize E3 ubiquitin ligase Smurf1 to downregulate TGF-β receptor level, which negatively regulate the TGF-β/Smad pathway [ 17 ]."

32442538

USP9X affects ITCH

1 | 4

USP9X deubiquitinates ITCH. 4 / 5

1 | 4

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"USP9X has been reported to simultaneously regulate endocytosis of the EGFR by deubiquitinating its endocytic adaptor Eps15 and ubiquitin ligase Itch in tumor cell lines (17, 18, 40)."

35389885

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"USP9X (FAM) deubiquitylates the autoubiquitylated E3 ligases Itch and SMURF1 and, thereby, increases their stability XREF_BIBR - XREF_BIBR."

24714733

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"USP9X has been shown to regulate EGFR endocytosis in tumor cell lines by deubiquitinating its endocytic adaptor Eps15 and ubiquitin ligase Itch [31]."

36653359

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"USP8 and USP9X deubiquitinate ITCH to induce ubiquitination and degradation of the anti-apoptotic protein c-FLIP, leading to apoptosis in glioblastoma [XREF_BIBR], or to anoikis in pancreatic ductal adenocarcinoma [XREF_BIBR]."

27203743

USP9X affects IQCB1

1 | 4

USP9X deubiquitinates IQCB1. 3 / 4

1 | 3

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"In fact, in growth-arrested conditions, USP9X is recruited at the centrosome, deubiquitylates NPHP5 and prevents its degradation and cilium disassembly (Das et al., 2017)."

35646931

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"Only wild type USP9X could robustly deubiquitinate NPHP5 (XREF_FIG)."

28498859

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"Because USP9X deubiquitinates NPHP5 (XREF_FIG), we hypothesize that NPHP5 is prone to ubiquitination when its association with USP9X is compromised in G2/M."

28498859

USP9X deubiquitinates IQCB1 on K48. 1 / 1

| 1

➶

reach

"On the basis of our findings that NPHP5 is deubiquitinated by USP9X, K48 ubiquitinated by MARCH7 and K63 ubiquitinated by BBS11, we asked whether simultaneous ablation of MARCH7 and/or BBS11 might override the effects of USP9X loss on NPHP5."

28498859

USP9X affects TTK

1 | 3

USP9X deubiquitinates TTK. 3 / 4

1 | 3

➶

reach

"The results suggested that knockdown of USP9X increased the ubiquitination of TTK protein (Figure 2E)."

29721084

➶

reach

"The results outlined above suggested that USP9X interacts with and deubiquitinates TTK for its stabilization."

29721084

➶

reach

"Knockdown of USP9X increased TTK ubiquitination, decreased TTK protein level, and suppressed cell proliferation, migration, invasion and tumor growth, demonstrating a phenotype similar to TTK depletion."

29721084

USP9X affects SOX2

1 | 3

USP9X deubiquitinates SOX2. 3 / 4

1 | 3

➶

reach

"Usp9x knockdown in melanoma increased SOX2 ubiquitination, leading to its depletion, and enhanced apoptotic effects of BRAF inhibitor and MEK inhibitors."

33613844

➶

reach

"Further investigation of the interaction between NGA and USP9x may provide information for optimizing more specific USP9x inhibitors.In summary, we demonstrate that USP9x can deubiquitinate and stabil[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

31605775

➶

reach

"We identified that Usp9x deubiquitinates SOX2 and can increaseSOX2 levels, but additional studies are needed to confirm the specific ubiquitin sites among the 16 lysine residues in SOX2 that could be putative ubiquitin acceptors."

33613844

USP9X affects RNF115

1 | 3

USP9X leads to the deubiquitination of RNF115. 3 / 4

1 | 3

➶

reach

"Biochemical evidence further indicated that depletion of USP9X increased, whereas overexpression of USP9X decreased, RNF115 ubiquitination (Figure 5)."

30689267

➶

reach

"Immunoblotting analysis showed that depletion of USP9X increased the ubiquitination of RNF115 protein (Figure 5E)."

30689267

➶

reach

"Conversely, overexpression of USP9X decreased RNF115 ubiquitination (Figure 5F)."

30689267

USP9X affects RIT1

| 4

USP9X deubiquitinates RIT1. 2 / 2

| 2

➶

reach

"Expression of wild-type USP9X reduced ubiquitination of RIT1 and RIT1 , but expression of USP9X did not affect RIT1 ubiquitination (Figure 4G)."

38077017

➶

reach

"Our findings suggest that USP9X deubiquitinates RIT1 , but we have yet to identify the E3 ubiquitin ligase(s) that is promoting ubiquitination."

38077017

USP9X deubiquitinates RIT1 on lysine. 1 / 1

| 1

➶

reach

"Given this, it is possible that USP9X deubiquitinates RIT1 at these lysine sites."

38077017

USP9X leads to the deubiquitination of mutated RIT1. 1 / 1

| 1

➶

reach

"USP9X deubiquitinates wild-type and mutant RIT1 (Figure 4F–G), thereby increasing RIT1 abundance and stability."

38077017

USP9X affects PEX5

1 | 3

USP9X deubiquitinates PEX5. 2 / 3

1 | 2

➶

reach

32442538

➶

reach

"The PEX1–PEX6 complex releases ubiquitinated PEX5 from the peroxisomal membrane to the cytosol, and PEX5 is deubiquitinated by USP9X in mammalian systems for the next cycle of transport (26–28)."

39398621

USP9X deubiquitinates PEX5. 1 / 1

| 1

➶

reach

"In addition, Pex5p can be deubiquitinated by the deubiquitinase USP9X [171] ."

26367801

USP9X affects NRP1

| 4

USP9X deubiquitinates NRP1. 4 / 4

| 4

➶

reach

"We found that USP9X was a critical deubiquitinating enzyme which primarily responsible for the NRP1 stability and NRP1 deubiquitination mediated by USP9X enhanced HSC activation."

36653359

➶

reach

"Given the preceding findings, we postulate that USP9X performs its function by deubiquitinating NRP1."

36653359

➶

reach

"Moreover, USP9X was found to be a critical deubiquitinating enzyme for the stability and high activity of NRP1 and NRP1 deubiquitination mediated by USP9X enhanced HSC activation and liver fibrosis."

36653359

➶

reach

"NRP1 deubiquitination mediated by USP9X enhances HSC activation, implying that targeting NRP1 or USP9X potentiates novel options in the treatment of liver fibrosis."

36653359

USP9X affects MAP3K5

1 | 3

USP9X deubiquitinates MAP3K5. 3 / 4

1 | 3

➶

reach

"USP9X also promoted apoptosis in HCC by deubiquitinating apoptotic signaling-regulating kinase (ASK1) and enhancing oxidative stress-induced JNK activation and cell death [70]."

35884607

➶

reach

"USP9X binds with and deubiquitinates ASK1, advancing the ASK1-p38/JNK pathway under oxidative stress conditions [115]."

35891784

➶

reach

"It has been reported that USP9X can deubiquitinate and stabilize ASK1 and ZBTB38 and therefore, antagonize the OSS damage [ 14 , 15 ]."

32442538

USP9X affects KRAS

| 4

USP9X deubiquitinates KRAS. 4 / 4

| 4

➶

reach

"These results collectively indicate that the 173-345 aa form of NDRG3 can exert a dominant-negative effect on the NDRG3/USP9X-mediated KRAS stabilization process by competing with intact NDRG3 protein for KRAS binding, thereby interfering with the deubiquitination of KRAS by USP9X."

39819877

➶

reach

"It becomes then important in future studies to finely elucidate the structural mechanism of the interaction between KRAS and C-terminal NDRG3, and devise ways to molecularly control it.In conclusion, we showed that KRAS protein is deubiquitinated by USP9X via the scaffolding function of NDRG3, promoting KRAS protein accumulation and KRAS-driven tumorigenesis."

39819877

➶

reach

"KRAS protein is deubiquitinated and stabilized by USP9X (Ubiquitin Specific Peptidase 9 X-Linked) via the scaffolding function of NDRG3."

39819877

➶

reach

"Also, the KRAS ubiquitination level that was highly reduced by USP9X overexpression returned to the normal level upon NDRG3 depletion (Fig. 5j and Supplementary Fig. 6b)."

39819877

USP9X affects KDM4C

1 | 3

USP9X leads to the deubiquitination of KDM4C. 3 / 4

1 | 3

➶

reach

"The deubiquitinase USP9X increases radiotherapy resistance of lung malignancy by promoting KDM4C deubiquitination and activating the TGF-β2/Smad pathway [ 36 ]."

36871813

➶

reach

"Our previous study found that the deubiquitinase USP9X could interact with the histone lysine demethylase 4 C (KDM4C) to mediate KDM4C deubiquitination and thus upregulate its protein expression, and aberrantly expressed KDM4C upregulated the transcriptional expression of TGF-β2 by directly reducing the level of histone H3K9me3 in the promoter region of TGF-β2, which in turn activated the Smad/ATM/Chk2 signaling pathway, promoting DNA damage repair and leading to lung cancer radioresistance [19]."

38802791

➶

reach

"USP9X enhances the deubiquitination of KDM4C to elevate radioresistance of lung cancer cells by activating the TGF‐β2/Smad signaling [12]."

39143031

USP9X affects GJA1

| 1 3

USP9X deubiquitinates GJA1. 4 / 4

| 1 3

➶

reach

"The following findings were observed : (1) Expression of USP9X was down-regulated in the kidney tissue of db/db diabetic mice; (2) overexpression of USP9X suppressed high glucose (HG)-induced expressions of EMT markers and extra cellular matrix (ECM) in NRK-52E cells; (3) depletion of USP9X further aggravated EMT process and ECM production in NRK-52E cells; (4) USP9X deubiquitinated Cx43 and suppressed its degradation to regulate EMT process; (5) USP9X deubiquitinated Cx43 by directly binding to the C-terminal Tyr 286 of Cx43."

33857489

➶

trips

"USP9X deubiquitinates connexin43 to prevent high glucose-induced epithelial-to-mesenchymal transition in NRK-52E cells."

33857489

➶

reach

"The results showed that ubiquitin-specific protease 9 X-chromosome (USP9X), a deubiquitylating enzyme, was a candidate of Cx43 binding proteins, and USP9X inhibited Cx43 ubiquitination."

35391932

➶

reach

"Sun et al. found that the deubiquitinating enzyme USP9X deubiquitinates Cx43 to inhibit the process of high glucose-induced EMT, which in turn inhibits renal tubulointerstitial fibrosis 79."

39113708

USP9X affects FBXW7

1 | 3

USP9X leads to the deubiquitination of FBXW7. 3 / 4

1 | 3

➶

reach

"USP9X inhibits FBXW7 autoubiquitination, thereby reducing the activity of its downstream substrate c-Myc and suppressing tumor formation in mice (Khan et al., 2018)."

39749199

➶

reach

"USP9X antagonized FBW7 ubiquitylation and protected mice from CRC."

29346117

➶

reach

"USP9X antagonized FBW7 ubiquitylation, and Usp9x deletion caused Fbw7 destabilization."

29346117

USP9X affects ETS1

1 | 3

USP9X leads to the deubiquitination of ETS1. 3 / 4

1 | 3

➶

reach

"A recent report demonstrated that USP9X prevents ETS1 ubiquitination and thereby stabilizes the protein [XREF_BIBR]."

28474232

➶

reach

"Since USP9x can prevent Ets-1 ubiquitination [57], WP1130 has been proposed as a potential pharmacological approach to target Ets-1 towards degradation [58]."

35789155

➶

reach

"Since the deubiquitinase USP9X can prevent Ets-1 ubiquitination and increase protein stability [57], WP1130, an inhibitor for USP9X can serve as a potential inhibitor of Ets-1 by promoting its degradation [58]."

35789155

USP9X affects CEP131

1 | 3

USP9X deubiquitinates CEP131. 3 / 4

1 | 3

➶

reach

"USP9X deubiquitinates CEP131."

28361952

➶

reach

"USP9X can modulate centrosome biogenesis and enhance breast carcinogenesis by deubiquitinating and stabilizing the centriolar satellite protein, CEP131 (40)."

37920433

➶

reach

"USP9X gain-of-function leads to CEP131 deubiquitylation, stabilisation and centrosome amplification [XREF_BIBR]."

28900014

USP9X affects BIRC5

| 4

USP9X deubiquitinates BIRC5. 3 / 3

| 3

➶

reach

"Previously, Chen et al. reported that USP9X is involved in deubiquitination and degradation of survivin by inhibition of long noncoding RNA LNC473 [41]."

32825566

➶

reach

"In addition to its functions in endocytosis, the human Faf homolog, Usp9, affects progression through mitosis by deubiquitinating the chromosomal passenger protein survivin [ 75 ]."

18346885

➶

reach

"Another DUB, USP9X, deubiquitinated and stabilized survivin protein, and contributed to cell proliferation and invasion in HCC cells via the long noncoding RNA LNC473 [64]."

35884607

USP9X deubiquitinates BIRC5 on lysine. 1 / 1

| 1

➶

reach

"Lysine 63 de-ubiquitination of survivin by hFAM is required for the dissociation of survivin from centromeres."

32410646

USP9X affects BCL9

1 | 3

USP9X deubiquitinates BCL9. 3 / 4

1 | 3

➶

reach

"Additionally, the deubiquitination of BCL9 by USP9X increases proliferation and invasion of breast cancer cells."

32486158

➶

reach

"278 The deubiquitination of BCL9 by USP9X facilitates the assembly of the β-catenin-BCL9-PYGO complex, thereby augmenting the transcriptional activity of Wnt/β-catenin target genes."

40034124

➶

reach

"The USP9X mediated BCL9 deubiquitination promotes formation of the beta, catenin, BCL9, and PYGO complex, increasing the transcriptional activity of the Wnt and beta-catenin target genes."

32486158

USP9X affects ALDH1A3

1 | 3

USP9X deubiquitinates ALDH1A3. 3 / 4

1 | 3

➶

reach

"USP9X deubiquitinates ALDH1A3 and maintains mesenchymal identity in glioblastoma stem cells."

30958800

➶

reach

"ALDH1A3 levels are also dysregulated at the protein level in glioma stem cells, where ubiquitin-specific protease 9X (USP9X) deubiquitinates ALDH1A3, leading to its increased stabilization and levels [82]."

36672441

➶

reach

"For example, Chen et al. reported that USP9X could deubiquitinate ALDH1A3 in glioblastoma22."

37151889

USP9X affects TP53

1 | 2

USP9X leads to the deubiquitination of TP53. 2 / 3

1 | 2

➶

reach

"On the contrary, another study was found that inhibition of the deubiquitinase USP9x promoted p53 ubiquitination and hence mitigated p53 levels however DOX sensitivity still came about in HCC cells."

29458788

➶

reach

"USP9X inhibited p53 ubiquitination mediated degradation."

28446729

USP9X affects STMN1

1 | 2

USP9X deubiquitinates STMN1. 2 / 3

1 | 2

➶

reach

"However, whereas USP9X deubiquitinates wild-type SMN protein, its mutated form is unaffected by USP9X, causing its rapid degradation, and thereby contributes to impaired neuronal growth and development [27]."

38716888

➶

reach

32442538

USP9X affects STIL

| 3

USP9X deubiquitinates STIL. 3 / 3

| 3

➶

reach

"To test whether USP9X deubiquitylates the STIL MD3 domain, we incubated immunoprecipitated full-length STIL or the MD3 domain of STIL with recombinant GST, GST-USP7, or GST fused to the catalytic domain of USP9X (USP9X CD)."

31197030

➶

reach

"As USP9X interacts with and deubiquitylates the MD3 domain (aa 715-988) of STIL and removal of the MD3 domain destabilized STIL, USP9X controls STIL levels via the MD3 antidegron of STIL."

31197030

➶

reach

"USP9X directly deubiquitylates STIL."

31197030

USP9X affects Parkinson Disease

| 3

USP9X leads to the deubiquitination of Parkinson Disease on L1. 3 / 3

| 3

➶

reach

"The results further validated our hypothesis that the highly expressed USP9X increased and decreased the deubiquitination and ubiquitination of PD‐L1, respectively, leading to its accumulation in OSCC cell lines.3.5 USP9X is critical in OSCC tumor growth."

29992764

➶

reach

"Taken together, these findings suggest that activated tumor signaling pathways vary in different tumor microenvironments.Interestingly, USP9X reduced the ubiquitination of PD‐L1 and stabilized its protein expression."

29992764

➶

reach

"Ubiquitin‐specific peptidase 9, X‐linked (USP9X) inhibited the ubiquitination and degradation of PD‐L1, thereby mediating the immune escape of OSCC."

29992764

USP9X affects PRC2_complex

| 3

USP9X deubiquitinates PRC2_complex. 3 / 3

| 3

➶

reach

"We report here that Usp9x deubiquitinates and stabilizes PRC2, acting as a gatekeeper to the switch in H3K27me3 deposition patterns during mouse development."

33767158

➶

reach

"Usp9x deubiquitinates and stabilizes PRC2."

33767158

➶

reach

"This finding led us to hypothesize that Usp9x deubiquitinates and stabilizes PRC2 components to drive H3K27me3 deposition."

33767158

USP9X affects NUAK1

1 | 2

USP9X deubiquitinates NUAK1. 2 / 3

1 | 2

➶

reach

"An investigation of the polyubiquitination of AMPK-RKs showed that the deubiquitinating enzyme USP9X (ubiquitin specific protease-9) modulates the deubiquitination of NUAK1 (AMPK related kinase 5) and MARK4 (microtubule-affinity-regulating kinase 4) in cells XREF_BIBR."

23029325

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reach

32442538

USP9X affects MTOR

1 | 2

USP9X deubiquitinates MTOR. 2 / 3

1 | 2

➶

reach

32442538

➶

reach

"USP9X deubiquitination of the mTOR (mechanistic target of rapamycin) signaling component RAPTOR protects it from proteasomal degradation, thus promoting mTOR signaling and proliferation of NSCs (34)."

35662507

USP9X affects MIB1

1 | 2

USP9X deubiquitinates MIB1. 2 / 3

1 | 2

➶

reach

"Further, in human breast cancer cell lines, USP9X deubiquitinates and stabilizes MIB1, an activator of ligand dependent canonical NOTCH1 signaling that is important for cardiac development."

33547080

➶

reach

"Therefore, we postulated that nitrosylated USP9X deubiquitinates and stabilizes MIB1 in valvular interstitial cells, which potentiates the ability of a ligand producing cell to activate NOTCH on a neighboring cell."

33547080

USP9X affects MARCHF7

1 | 2

USP9X deubiquitinates MARCHF7. 2 / 3

1 | 2

➶

reach

"Exogenous expression and short interfering RNA depletion experiments demonstrate that MARCH7 can be stabilized by both USP9X and USP7, which deubiquitylate MARCH7 in the cytosol and nucleus, respectively."

18410486

➶

reach

"Previously, MARCH7 was reported to be stabilized by Ubiquitin Specific Peptidase 9 X-Linked (USP9X) and Ubiquitin Specific Peptidase 7 (USP7), which deubiquitylate MARCH7 in the cytosol and nucleus, respectively [27]."

38462600

USP9X affects IGF1R

| 3

USP9X deubiquitinates IGF1R. 3 / 3

| 3

➶

reach

"We found that USP9X interacted with IGF-IR, and that knockdown of USP9X decreases IGF-IR protein level and increased ubiquitination of IGF-IR."

30338032

➶

reach

"These results raise the possibility that USP9X deubiquitinates IGF-IR to prevent its degradation."

30338032

➶

reach

"Furthermore, knockdown of USP9X significantly increased IGF-IR ubiquitination in HEK293T cells."

30338032

USP9X affects EGLN3

1 | 2

USP9X deubiquitinates EGLN3. 2 / 3

1 | 2

➶

reach

"In cholangiocarcinoma (CCA), the tumor suppressor KIF1Bβ induced apoptosis and was up-regulated by Egl nine homolog 3 (EGLN3), and ubiquitin-specific peptidase 9X (USP9X) acted to de-ubiquitinate and stabilize EGLN3 thereby accelerating this process."

38433242

➶

reach

"USP9X exerts its tumor-suppressive functions through deubiquitinating Egl-9 family hypoxia inducible factor 3, thereby activating the apoptosis signaling pathway components, kinesin KIF1Bβ and cleaved caspase-3 (57)."

37920433

USP9X affects CDC20

| 3

USP9X deubiquitinates CDC20. 3 / 3

| 3

➶

reach

"In summary, the data presented here show that USP9X antagonizes Cdc20 auto-ubiquitination and degradation to limit the turnover of MCC complexes by APC/C."

29669289

➶

reach

"We hypothesize that USP9X deubiquitinates Cdc20 directly; however, we can not rule out the possibility that USP9X loss enhances Cdc20 ubiquitination and degradation indirectly."

29669289

➶

reach

"Interestingly, it has been shown that deubiquitinase ubiquitin‐specific peptidase 9 X‐linked (USP9X) could inhibit ubiquitination and degradation of Cdc20, thus reinforcing the SAC."

36967563

USP9X affects BCL10

1 | 2

USP9X deubiquitinates BCL10. 2 / 3

1 | 2

➶

reach

"Finally, the ubiquitin specific protease 9X (USP9X) interacts with BCL10 in activated T cells and silencing of USP9X augments BCL10 ubiquitination and impairs NF-kappaB signaling in T cells."

30022982

➶

reach

32442538

USP9X affects ANK3

| 3

USP9X deubiquitinates ANK3. 2 / 2

| 2

➶

reach

"USP9X deubiquitination of ANK3 (and other synaptic proteins including ANK2, SHANK3, and TNKS2) is required to antagonize its proteasomal degradation and is essential for synapse formation (30)."

35662507

➶

reach

"Usp9X can reduce the level of polyubiquitination of ankyrin-G and stabilize it to maintain dendritic spine development [20]."

38632655

Phosphorylated USP9X leads to the deubiquitination of ANK3. 1 / 1

| 1

➶

reach

"Phosphorylation of Usp9X enhances their interaction, reduces ankyrin-G polyubiquitination, and stabilizes ankyrin-G for the maintenance of dendritic spine development [167]."

36430976

USP9X affects AMOTL2

1 | 2

USP9X deubiquitinates AMOTL2. 2 / 3

1 | 2

➶

reach

"These results indicate that deubiquitination of AMOTL2 by USP9X depresses LATS1/2 activity and subsequently activates YAP."

29366444

➶

reach

"Importantly, USP9X depletion increased AMOTL2 mono-ubiquitination, an effect that was abolished by co-depletion of WWP1 using two independent small hairpin RNAs (shRNAs), confirming that the two enzymes indeed exhibit contrasting functions on the same AMOTL2 lysine residues (Fig S2B)."

34404733

USP9X affects α-synuclein

| 2

USP9X deubiquitinates α-synuclein. 2 / 2

| 2

➶

reach

"Indeed, Rott et al. [79] showed that purified USP9X reduced the level of α-synuclein mono-ubiquitination, which reduced the number of α-synuclein inclusions and decreased toxicity, whereas USP9X KD increased this."

36831318

➶

reach

"Similarly, USP9X deubiquitinated α-synuclein; however, the exact effects on α-synuclein clearance and aggregation are still unclear."

36831318

USP9X affects epnA

| 2

USP9X deubiquitinates epnA. 2 / 2

| 2

➶

reach

"It was recently shown that silencing Fam by siRNA abrogated ionomycin induced decrease in Epsin ubiquitylation, indicating that Fam plays a role in regulating levels of Epsin ubiquitylation [15]."

15694383

➶

reach

"However, in vitro data on direct deubiquitylation of Epsin by Fam are lacking, and the ~ 50% identity between Faf and Fam suggests different specificities for substrates [49]; indeed, the only reporte[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

15694383

USP9X affects TRRAP

| 2

USP9X deubiquitinates TRRAP. 2 / 2

| 2

➶

reach

"USP9X deubiquitinates TRRAP to promote glioblastoma cell proliferation and migration and M2 macrophage polarization."

39073416

➶

reach

"Together, USP9X deubiquitinated TRRAP, thereby promoting glioblastoma cell proliferation, migration, and M2 macrophage polarization."

39073416

USP9X affects RICTOR

1 | 1

USP9X leads to the deubiquitination of RICTOR. 1 / 2

1 | 1

➶

reach

"Conversely, overexpression of USP9X in HEK293 cells decreased RICTOR ubiquitination ( Figure 3 D); increased phosphorylation of AKT at Ser473, without affecting phosphorylation of AKT-Thr308 or S6K ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

33378666

USP9X affects REV1

| 2

USP9X leads to the deubiquitination of REV1. 2 / 2

| 2

➶

reach

"Protein stability, in vitro ubiquitination level assays, and protein half-life experiments confirmed that USP9X can downregulate the ubiquitination of REV1, which positively regulates REV1 protein expression."

38802791

➶

reach

"USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance."

38802791

USP9X affects PRKAA2

| 2

USP9X leads to the deubiquitination of PRKAA2. 2 / 2

| 2

➶

reach

"As expected, overexpression of USP9X reduced ubiquitination of PRKAA2 (Figure 7A)."

35390516

➶

reach

"In our study, we identified USP9X as a novel deubiquitinase of PRKAA2 based on the following evidence: (1) USP9X interacted with PRKAA2; (2) USP9X significantly reduced the ubiquitination of PRKAA2; and (3) a loss-of-function mutant of USP9X as well as USP9X inhibitor WP1130 abolished its deuibiquitinating activity on PRKAA2."

35390516

USP9X affects PEG10

| 2

USP9X deubiquitinates PEG10. 2 / 2

| 2

➶

reach

"Ubiquitin-specific protease 9X (USP9X), a deubiquitinase, interacted with and deubiquitinated PEG10, thereby stabilizing PEG10."

38677662

➶

reach

"PEG10 deubiquitination by USP9X appeared to stabilize PEG10-RF1 specifically because USP9X-deficient ESCs contained less PEG10-RF1 than control ESCs, whereas the amount of PEG10-RF1/2 was largely unaltered (Fig 1B and 1G)."

30951545

USP9X affects PEF1

| 2

USP9X deubiquitinates PEF1. 1 / 1

| 1

➶

reach

"As USP9X, but not USP9X , deubiquitylated PEF1 in vitro (Figure 6G), we conclude that PEF1 ubiquitylation is removed by USP9X."

35120648

Ubiquitinated USP9X leads to the deubiquitination of PEF1. 1 / 1

| 1

➶

reach

"In vitro ubiquitylation and USP9X-mediated deubiquitylation of PEF1."

35120648

USP9X affects OGT

| 2

USP9X leads to the deubiquitination of OGT. 2 / 2

| 2

➶

reach

"In this report, we demonstrated that the arginine methylation of OGT by CARM1 enhanced the stability of OGT through binding of USP9X, which inhibited the polyubiquitination of OGT in NSCLC cells."

39715739

➶

reach

"The OGT R348K mutant showed higher levels of ubiquitination than OGT WT, and knockdown of USP9X increased the ubiquitination of OGT WT, but not that of the OGT R348K mutant (Fig. 4E)."

39715739

USP9X affects MBD2

| 2

USP9X deubiquitinates MBD2 on lysine. 1 / 1

| 1

➶

reach

"USP9X deubiquitinates Histone lysine demethylase 4 C, overexpression of which is associated with poor prognosis and radioresistance in lung cancer and is associated with poor survival in non-small cell lung cancer, further supporting the possibility that USP9X is an oncogene [146, 147]."

38453895

USP9X deubiquitinates MBD2. 1 / 1

| 1

➶

reach

38453895

USP9X affects MARK4

1 | 1

USP9X leads to the deubiquitination of MARK4. 1 / 2

1 | 1

➶

reach

23029325

USP9X affects LATS2

1 | 1

USP9X deubiquitinates LATS2. 1 / 2

1 | 1

➶

reach

"We further demonstrated that USP9X deubiquitinates LATS2 and thus prevents LATS2 degradation by the proteasome."

29183995

USP9X affects Histone

| 2

USP9X deubiquitinates Histone on lysine. 1 / 1

| 1

➶

reach

38453895

USP9X deubiquitinates Histone. 1 / 1

| 1

➶

reach

38453895

USP9X affects F2R

| 2

USP9X deubiquitinates F2R. 2 / 2

| 2

➶

reach

"FAF clearly reduced poly-ubiquitinated PAR-1 level in vitro (XREF_FIG), supporting that FAF directly de-ubiquitinates PAR-1."

23271647

➶

reach

"To test whether FAF directly de-ubiquitinates PAR-1, we used affinity purified FAF and HA-Ub-labelled PAR-1 in an in vitro reaction."

23271647

USP9X affects EPN

| 2

USP9X deubiquitinates EPN. 2 / 2

| 2

➶

reach

"Studies have shown that USP9X mediates epsin-specific deubiquitination to regulate vesicle trafficking (17)."

35389885

➶

reach

"Agonist stimulation of Notch leads to the recruitment of USP9X, a deubiquitinating enzyme, which deubiquitinates epsin and enables it to promote Notch internalization."

21438117

USP9X affects EIF4A1

1 | 1

USP9X deubiquitinates EIF4A1. 1 / 2

1 | 1

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reach

"These data suggested that the deubiquitination of eIF4A1 by USP9X is required for eIF4A1 protein stability."

29228324

USP9X affects E3_Ub_ligase

| 2

USP9X deubiquitinates E3_Ub_ligase. 2 / 2

| 2

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reach

"However, Xie et al. found that USP9X can deubiquitinate and stabilize E3 ubiquitin ligase Smurf1 to downregulate TGF-β receptor level, which negatively regulate the TGF-β/Smad pathway [ 17 ]."

32442538

➶

reach

"USP9X reduces VHL abundance by deubiquitylating SMURF1, an E3 ligase targeting VHL [39] ."

31706510

USP9X affects Cyclin

| 2

USP9X deubiquitinates Cyclin on D1. 1 / 1

| 1

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reach

"USP9X overexpression could promote WP1130-mediated USP9X, CCND1, and SOX11 protein levels, indicating that USP9X exerts its function by deubiquitinating Cyclin D1 and/or SOX11."

35865393

USP9X deubiquitinates Cyclin. 1 / 1

| 1

➶

reach

"USP9X overexpression could promote WP1130-mediated USP9X, CCND1, and SOX11 protein levels, indicating that USP9X exerts its function by deubiquitinating Cyclin D1 and/or SOX11."

35865393

USP9X affects BRCA1

1 | 1

USP9X leads to the deubiquitination of BRCA1. 1 / 2

1 | 1

➶

reach

"Immunoblotting analysis showed that USP9X knockdown significantly increased the ubiquitination of BRCA1 protein (Figure 2D).3.3 USP9X interacts with BRCA1."

31512408

USP9X affects BMAL1

1 | 1

USP9X leads to the deubiquitination of BMAL1. 1 / 2

1 | 1

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reach

"Through biochemical experiments, we discover that USP9X reduces BMAL1 ubiquitination, enhances its stability, and increases its protein level, leading to the elevated transcriptional activity."

29626158

USP9X affects α-Synuclein

| 1

USP9X deubiquitinates α-Synuclein. 1 / 1

| 1

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reach

"This is because Usp9x deubiquitinates α-Synuclein and can thus modulate microtubule-associated protein tau (MAPT) phosphorylation."

38150994

USP9X affects pygo

| 1

USP9X leads to the deubiquitination of pygo. 1 / 1

| 1

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reach

"The USP9X mediated BCL9 deubiquitination promotes formation of the beta, catenin, BCL9, and PYGO complex, increasing the transcriptional activity of the Wnt and beta-catenin target genes."

32486158

USP9X affects lqf

| 1

USP9X deubiquitinates lqf. 1 / 1

| 1

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reach

"Deubiquitination of lqf by faf increases lqf activity, probably by preventing an inhibitory effect of ubiquitination of lqf."

18845146

USP9X affects glioblastoma22

| 1

USP9X deubiquitinates glioblastoma22. 1 / 1

| 1

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reach

"For example, Chen et al. reported that USP9X could deubiquitinate ALDH1A3 in glioblastoma22."

37151889

USP9X affects core PRC2 members

| 1

USP9X deubiquitinates core PRC2 members. 1 / 1

| 1

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reach

"In summary, we report here that Usp9x deubiquitinates core PRC2 members to promote high levels of H3K27me3, repress developmental regulatory genes and maintain a preimplantation like phenotype in ES cells."

33767158

USP9X affects connexin43

| 1

USP9X deubiquitinates connexin43. 1 / 1

| 1

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reach

"However, USP9X was reported to be lowly expressed in the kidney of DKD mice and USP9X overexpression deubiquitinates connexin43 to weaken the fibrosis of high glucose (HG)-induced renal cells [15]."

39967230

USP9X affects alpha-syn

| 1

USP9X deubiquitinates alpha-syn. 1 / 1

| 1

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reach

"Remarkably, de-ubiquitination of alpha-syn by USP9X determines the partition of alpha-syn between the UPS and autophagy pathways."

32344772

USP9X affects TNBC

| 1

USP9X deubiquitinates TNBC. 1 / 1

| 1

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reach

"Mechanistically, RPS27A, as an upstream adaptor, recruited USP9X to deubiquitinate PPP1R14B and facilitate upregulation of PPP1R14B in TNBC."

36484700

USP9X affects TMPRSS2

| 1

USP9X deubiquitinates TMPRSS2. 1 / 1

| 1

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reach

"USP9X binds to the ETS domain in ERG protein; therefore, USP9X deubiquitinates and stabilizes full-length ERG and TMPRSS2 - ERG fusion gene products."

30217566

USP9X affects TGFBR2

| 1

USP9X deubiquitinates TGFBR2. 1 / 1

| 1

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reach

"Mechanically, USP9X positively influences the expression of TGFBR2 at different levels through two independent ways: (i) directly targets and deubiquitinates TGFBR2, which maintains the protein stability of TGFBR2 through avoiding degradation mediated by ubiquitin-proteasome system; (ii) indirectly maintains TGFBR2 messenger RNA (mRNA) expression via SMAD4/miR-143 axis."

35578792

USP9X affects TGFBR1

| 1

USP9X deubiquitinates TGFBR1. 1 / 1

| 1

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reach

"Similarly, USP9x and USP11 interact and deubiquitinate Smad4 and ALK5, respectively, [29, 30] to regulate the transforming growth factor/BMP cell signaling pathways necessary for osteogenic differentiation and bone formation."

35273362

USP9X affects TCF4

| 1

USP9X deubiquitinates TCF4. 1 / 1

| 1

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reach

"USP9 has also been implicated in deubiquitinating TCF4, promoting its stability and allowing it to regulate target genes."

37863330

USP9X affects TBL1XR1

| 1

USP9X deubiquitinates TBL1XR1. 1 / 1

| 1

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reach

"Moreover, USP9X deubiquitinated TBL1XR1 to regulate TBL1XR1 expression."

39841820

USP9X affects STUB1

| 1

USP9X leads to the deubiquitination of STUB1. 1 / 1

| 1

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reach

"Like PHF-tau, mono- or polyubiquitination involves CHIP, whereas USP9X leads to the deubiquitination of CHIP-monoubiquitinated α-synuclein [48]."

35406655

USP9X affects STAM

| 1

USP9X deubiquitinates STAM. 1 / 1

| 1

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reach

"In addition, we identified STAM and NFX1, which are known to be deubiquitylated by USP8 and USP9 respectively."

33417828

USP9X affects SOX9

| 1

USP9X leads to the deubiquitination of SOX9. 1 / 1

| 1

➶

reach

"In accordance with the effect of USP9X deficiency, pharmacological inhibition of USP9X by WP1130 increased the polyubiquitination of SR-A1 (Supplemental Figure 5C)."

35389885

USP9X affects SOX11

| 1

USP9X deubiquitinates SOX11. 1 / 1

| 1

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reach

"USP9X overexpression could promote WP1130-mediated USP9X, CCND1, and SOX11 protein levels, indicating that USP9X exerts its function by deubiquitinating Cyclin D1 and/or SOX11."

35865393

USP9X affects SNRPN

| 1

USP9X deubiquitinates SNRPN. 1 / 1

| 1

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reach

"Usp9x deubiquitinates SMN that is mostly mono- and di ubiquitinated."

23112048

USP9X affects SNAI1

| 1

USP9X deubiquitinates SNAI1. 1 / 1

| 1

➶

reach

"Here, we demonstrate that the deubiquitinating enzyme USP9X deubiquitinates and stabilizes Snail1, thereby promoting metastasis and chemoresistance."

35506169

USP9X affects SLC7A11

| 1

USP9X leads to the deubiquitination of SLC7A11. 1 / 1

| 1

➶

reach

"Besides, USP9X is previously suggested to mediate SLC7A11 deubiquitination (Fig. 3F)."

39656358

USP9X affects RPTOR

| 1

USP9X leads to the deubiquitination of RPTOR. 1 / 1

| 1

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reach

"The increased Raptor protein observed in the hippocampus of P301S mice was likely attributable to elevated USP9X content, which enhanced Raptor deubiquitination and protected it from proteasomal degradation."

39449082

USP9X affects Proteasome

| 1

USP9X leads to the deubiquitination of Proteasome. 1 / 1

| 1

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reach

"Similarly, Glycogen synthase kinase-3β (GSK-3β), often dysregulated in many types of cancer, has been shown to promote ubiquitination and proteasome-dependent degradation of ASK1 by inhibition of ubiq[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

28552579

USP9X affects PRICKLE2

| 1

USP9X deubiquitinates PRICKLE2. 1 / 1

| 1

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reach

"[XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR] We postulated the physical interaction between the PRICKLEs and USP9X might indicate that PRICKLE was a USP9X substrate, and that USP9X deubiquitinates and stabilizes both PRICKLE1 and PRICKLE2."

25763846

USP9X affects PRICKLE1

| 1

USP9X deubiquitinates PRICKLE1. 1 / 1

| 1

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reach

25763846

USP9X affects PRICKLE

| 1

USP9X deubiquitinates PRICKLE. 1 / 1

| 1

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reach

"PRICKLE and USP9X interact through their carboxy-termini; and USP9X de-ubiquitinates PRICKLE, protecting it from proteasomal degradation."

25763846

USP9X affects PBX1

| 1

USP9X deubiquitinates PBX1. 1 / 1

| 1

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reach

"Mutations or imbalances in the ubiquitination/deubiquitination signaling pathway in prostate cancer led to abnormalities of the deubiquitinase USP9X, which was also responsible for deubiquitinating PBX1 [41]."

39289660

USP9X affects OTUB1

| 1

USP9X deubiquitinates OTUB1. 1 / 1

| 1

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reach

"Moreover, USP9X, USP8, and CSN5 can deubiquitinate PD-L1, and OTUB1 increase PD-L1 levels by preventing new synthetic PD-L1 from entering the ERAD."

38715050

USP9X affects NFX1

| 1

USP9X deubiquitinates NFX1. 1 / 1

| 1

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reach

"In addition, we identified STAM and NFX1, which are known to be deubiquitylated by USP8 and USP9 respectively."

33417828

USP9X affects MKI67

| 1

USP9X deubiquitinates MKI67. 1 / 1

| 1

➶

reach

"NO has been identified as a calcification inhibitor and exerted its function through the activation of NOTCH signaling pathway, An proteomic approach has proved that S‐nitrosylation of ubiquitin‐specific peptidase 9, X‐linked (USP9X) could deubiquitinate and stabilize MIB1 for NOTCH signaling pathway activation during the progress of VC."

36620697

USP9X affects MCL-1 [

| 1

USP9X leads to the deubiquitination of MCL-1 [. 1 / 1

| 1

➶

reach

"Ubiquitin specific peptidase 9 X linked, USP9X, reverses ubiquitination of MCL-1 [XREF_BIBR]."

23958396

USP9X affects MARCH

| 1

USP9X deubiquitinates MARCH. 1 / 1

| 1

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reach

32442538

USP9X affects Liquid facets

| 1

USP9X leads to the deubiquitination of Liquid facets. 1 / 1

| 1

➶

reach

"The study in fly Drosophila indicates that Fat facets (Usp9 ortholog) promotes endocytosis of Delta by deubiquitylating Liquid facets (Epsin ortholog) XREF_BIBR - XREF_BIBR."

24714733

USP9X affects Integrins

| 1

USP9X deubiquitinates Integrins. 1 / 1

| 1

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reach

"Immunostaining and proteomics analysis indicate that the USP12/46-WDRs complex-mediated Itgb1 deubiquitination occurs at endosomes, as neither our immunostainings nor previous studies on the adhesome composition found the complex in integrin adhesion sites.The genetic as well as poximitome screenings neither identified USP9X nor USP10, which have been reported to deubiquitinate α5β1 integrins (Gillespie et al, 2017; Kharitidi et al, 2015)."

39506038

USP9X affects Integrin α5

| 1

USP9X deubiquitinates Integrin α5. 1 / 1

| 1

➶

reach

"Integrin α5β1 was found to be deubiquitinated by ubiquitin specific peptidase 9× (USP9x) ( Kharitidi et al., 2015 )."

37245545

USP9X affects ITGB1

| 1

USP9X deubiquitinates ITGB1. 1 / 1

| 1

➶

reach

"As USP9X was shown to deubiquitinate Itga5 tails on endosomes following soluble FN stimulation (Kharitidi et al, 2015), we first investigated whether USP9X also deubiquitinates and stabilizes Itgb1 in cells cultured under steady-state conditions."

39506038

USP9X affects ITGA5

| 1

USP9X deubiquitinates ITGA5. 1 / 1

| 1

➶

reach

"Although integrin deubiquitination has not been investigated in this report, Kharitidi and colleagues showed in an independent study that USP9X can deubiquitinate the α5-subunit (Itga5) in cells upon treatment with soluble FN (Kharitidi et al, 2015)."

39506038

USP9X affects IRS1

| 1

USP9X deubiquitinates IRS1. 1 / 1

| 1

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reach

"On the other hand, the reduction of IRS-1 protein level was relatively small, suggesting that deubiquitination of IRS-1 by USP9X is not so active as for IRS-2."

30338032

USP9X affects IGF2BP2

| 1

USP9X deubiquitinates IGF2BP2. 1 / 1

| 1

➶

reach

"Furthermore, USP9X contributed to promoting the onset of UC and that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was deubiquitinated by USP9X."

39435543

USP9X affects FN1

| 1

USP9X leads to the deubiquitination of FN1. 1 / 1

| 1

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reach

"Importantly, USP9x depletion augmented and maintained the FN induced integrin alpha5beta1 complex ubiquitination and led to a slower migration rate, suggesting that USP9x contributes to deubiquitinati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

26456826

USP9X affects FANCD2

| 1

USP9X deubiquitinates FANCD2. 1 / 1

| 1

➶

reach

16455486

USP9X affects F3

| 1

USP9X deubiquitinates F3. 1 / 1

| 1

➶

reach

"Usp9x deubiquitinates and stabilizes the TF, ERG, in prostate, and we previously published that DUB inhibitor (WP1130) has anti-tumor activity in ERG fusion driven prostate cancer [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

33613844

USP9X affects Egl-9

| 1

USP9X deubiquitinates Egl-9. 1 / 1

| 1

➶

reach

37920433

USP9X affects EGFR

| 1

USP9X leads to the deubiquitination of EGFR. 1 / 1

| 1

➶

reach

"However, silencing of USP9X did not increase EGFR ubiquitination, arguing that the receptor itself is not the direct target."

26748853

USP9X affects Deubiquitinase

| 1

USP9X deubiquitinates Deubiquitinase. 1 / 1

| 1

➶

reach

"Interestingly, LGALS9 can associate with the USP9X deubiquitylating enzyme (DUB) (Figure 2), an interaction that is lost upon lysosomal damage, and depletion of USP9X in cells lacking LGALS9 results in rescue of lysosomal ubiquitylation [29] (Figure 3)."

36713230

USP9X affects DVL

| 1

USP9X deubiquitinates DVL. 1 / 1

| 1

➶

reach

"Dvl is ubiquitinated by NEDL1, KLHL12, NEDD4L, Huwe1, Inversin, and ITCH and deubiquitinated by CYLD, USP9X, and USP14 (Miyazaki et al. 2004; Angers et al. 2006; Tauriello et al. 2010; Wei et al. 2012; Ding et al. 2013; Jung et al. 2013; de Groot et al. 2014; Nielsen et al. 2019)."

38383910

USP9X affects CDC123

| 1

USP9X deubiquitinates CDC123. 1 / 1

| 1

➶

reach

"USP9X deubiquitinates and stabilizes CDC123 to promote breast carcinogenesis through regulating cell cycle."

37314216

USP9X affects AURKB

| 1

USP9X deubiquitinates AURKB. 1 / 1

| 1

➶

reach

"NSFL1C promotes USP9X-mediated deubiquitination of AURKB to stabilize centromeric AURKB.."

37934606

USP9X affects ASK1 Δ

| 1

USP9X leads to the deubiquitination of ASK1 Δ. 1 / 1

| 1

➶

reach

"Moreover, ubiquitination of ASK1 ΔGG but not ASK1 WT was no more enhanced by USP9X knockdown ( Figure S11 )."

20005844

USP9X affects APC_C

| 1

USP9X leads to the deubiquitination of APC_C. 1 / 1

| 1

➶

reach

"Because USP9X is a DUB and the SAC signal relies on inhibition of the APC/C ubiquitin ligase, USP9X might antagonize APC/C dependent ubiquitination to help maintain the SAC."

29669289

USP9X affects AMPKα2

| 1

Mutated USP9X leads to the deubiquitination of AMPKα2. 1 / 1

| 1

➶

reach

"USP9X inhibitor WP1130 and loss-of-function USP9X mutation augmented the ubiquitination of AMPKα2."

35461795

USP9X affects ALKBH3

| 1

USP9X deubiquitinates ALKBH3. 1 / 1

| 1

➶

reach

"Instead, it seemed to act as a scaffold protein, recruiting two further DUBs, USP7 and USP9x, which then de-ubiquitylated ALKBH3."

26588485