IndraLab

Statements

USP6 affects MYH9

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USP6 binds MYH9. 10 / 57

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"Ericson-Johnson et al ( xref ) have proved USP6 rearrangements with the formation of the fusion gene MYH9-USP6 occur in most examples of NF."

31531104

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"The MYH9-USP6 fusion gene was detected by reverse transcription polymerase chain reaction (RT-PCR)[ xref ]."

39816285

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"Recently, however, the involvement of the MYH9-USP6 fusion gene has been suggested and the tumorigenic aspect of the disease has attracted attention [ xref ]."

39816285

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"Most of the fusion products in nodular fasciitis are MYH9-USP6 [ xref ]."

38022190

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"USP6 gene rearrangement, particularly MYH9-USP6 fusion, was present in the majority of cases."

39573982

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"Moreover, even cases of nodular fasciitis with typical MYH9::USP6 fusion can morphologically mimic sarcomatous growth and be easily misdiagnosed as malignancy."

36828621

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"Thirteen (68%) showed typical MYH9::USP6 fusions ( xref )."

36828621

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"Fluorescence in situ hybridization results in one of the patients revealed that the USP6 gene had been rearranged by the t(17;22)(p13;q12.3)MYH9-USP6 isochromosomal translocation."

37730564

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"Nodular fasciitis is characterized by a MYH9::USP6 gene fusion [ xref ], which occurs in the majority of cases."

39576105

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"We detected a MYH9-USP6 fusion in the two hip cases and a COL1A1-USP6 fusion in the shoulder case."

33404853

USP6 activates NFkappaB. 10 / 31

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"The upregulation of USP6 expression is considered to initiate osteoblastic tumorigenesis by triggering NF-kappa-B activation and contributing to the osteolytic and inflammatory processes typically obs[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

28449806

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

22081069

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"In aggregate these data indicate that TRE17(long) activates classical NF-κB through a mechanism that does not appear to involve phosphorylation and degradation of IκB."

22081069

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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."

22081069

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"In the current study we examine the mechanism by which it functions, demonstrating that TRE17 activates classical NF-κB through an atypical mechanism that is independent of IκB degradation."

22081069

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

22081069

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"However, the mechanism by which TRE17 activates NF-κB and the selective involvement of the classical vs. non-canonical pathways were not examined."

22081069

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"To determine whether TRE17 activates classical or non-canonical NF-κB, electrophoretic mobility shift assays (EMSAs) were performed."

22081069

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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."

22081069

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"We next sought to determine which IKK subunits were required for activation of NF-κB by TRE17."

22081069

USP6 affects Neoplasms

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USP6 activates Neoplasms.

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USP6 activates Neoplasms. 10 / 22

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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."

33775935

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"[USP6 induced neoplasm and their clinicopathological and genetic advances]."

35249300

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"In addition, USP6 could also drive the growth of xenograft tumors through activating Wnt signaling pathway [ 9 ]."

30297112

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"We therefore propose a model for the pathogenesis of TRE17-driven tumors in which TRE17 increases CD147 at the cell surface by preventing its lysosomal degradation, which in turn enhances MMP synthesis and matrix degradation, thereby promoting tumor cell invasion."

35926707

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"Recurrent USP6 rearrangements, specifically MYH9-USP6 fusion, have been identified in majority of nodular fasciitis cases, which defines primary ABC and nodular fasciitis as the biologic spectrum of U[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30553465

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"Previously, it was believed to occur as a reaction to trauma or as a reactive lesion caused by an underlying vascular event, but in recent years, it has been considered a true neoplasm caused by rearrangement of the ubiquitin-specific peptidase 6 (USP6) gene."

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"For example, Madan et al. showed that the USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds and inhibition of Wnt signaling significantly decreased the growth of USP6-driven xenograft tumors [20]."

36474192

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"However, a USP6 gene rearrangement study is of help in differentiating them because ABC is a true neoplasm-inducing USP6 gene rearrangement."

38335421

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"USP6 functions as a deubiquitinase and a designated oncogene, responsible for various cancers and sarcomas progression.USP6 modulates key pathways like NF-κB, JAK-STAT and Wnt/β-catenin driving tumor progression and inflammation.USP6 is implicated in a variety of cell biological processes, including cell cycle regulation, proliferation, invasion, migration, and DNA damage repair."

40348771

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"To further determine the role of Wnt signaling in USP6-mediated tumor growth, they tested USP6/NIH 3T3 cells with DKK1, a secreted protein that inhibits Fzd receptor activation."

40348771

USP6 inhibits Neoplasms.

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USP6 inhibits Neoplasms. 5 / 5

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"In sum, these results indicate that USP6 is sufficient to drive intratumoral activation of NK cells in Ewing sarcoma in vivo, and that NK cells are required for suppression of tumor growth by USP6."

37615015

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"Here, we demonstrate an essential role for NK cells in USP6-mediated tumor suppression."

37615015

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"Strikingly, we observed that USP6 inhibited growth of Ewing sarcoma tumors when xenografted into nude but not NOD scid gamma (NSG) mice, implicating a role for the innate immune system in mediating the tumor-suppressive function of USP6 (20)."

37615015

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"NK Cells are Required for Suppression of Ewing Sarcoma Tumor Growth by USP6."

37615015

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"We previously demonstrated that USP6 inhibits growth of Ewing sarcoma tumors when xenografted into nude mice, but not NSG mice (20)."

37615015

USP6 affects STAT3

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USP6 activates STAT3.

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USP6 activates STAT3. 10 / 19

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

27440725

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"Jak1 is required for STAT3 activation by USP6, and both are required for USP6-mediated cell survival and tumorigenesis."

27440725

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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."

27440725

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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."

27440725

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"Henrich and Coll showed that USP6 modulates the IFN (interferon) response in ES cells by potentiating the activation of STAT1 and STAT3 [184] ."

34678225

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"Cells lacking JAK1 (USP6/TRE17) showed no activation of STAT3 caused by USP6."

40348771

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"JAK1 levels in this clone were similar to those in control NIH3T3 cells, indicating that USP6’s activation of STAT3 requires JAK1 overexpression."

40348771

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"In these models, activation of STAT3, NF-κB, and β-catenin by USP6 was essential for tumorigenesis, as genetic or pharmacologic inhibition of these pathways significantly attenuated xenograft growth ( xref , xref , xref )."

33558334

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"USP6 activates STAT3 in cellular models and USP6 translocated tumors."

27440725

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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."

27440725

USP6 phosphorylates STAT3.

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USP6 phosphorylates STAT3. 3 / 3

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"A pan-Jak inhibitor completely blocked USP6-induced phosphorylation of STAT3, while the pan-Src PP2 inhibitor was ineffectual ( xref )."

27440725

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"As shown in xref , the pan-Jak inhibitor blocked USP6-induced phosphorylation of STAT3 in a dose-dependent manner, but had no effect on tyrosine phosphorylation induced by Src or the EGF receptor."

27440725

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"USP6-induced STAT3 phosphorylation was completely abrogated in cells depleted of Jak1 (USP6/J1#17)."

27440725

USP6 affects COL1A1

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USP6 binds COL1A1. 10 / 20

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"Among 11 IMTs with no kinase gene rearrangement identified, one tumour demonstrated ALK activation via gene amplification and overexpression, and another neoplasm carried COL1A1::USP6 translocation."

37071060

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"In 6/7 cases RNASeq showed a COL1A1-USP6 fusion."

32157177

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"Previous cytogenetic with subsequent RNA sequencing studies xref , xref in two STABCs showed COL1A1-USP6 fusion involving exon 1 of COL1A1 and a splicing variant of USP6 exon 1 or exon 2."

32157177

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"Majority of cases show COL1A1–USP6 fusion and herein we have described an additional case with ANGPTL2 gene as a novel fusion partner with USP6 ."

32157177

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"We detected a MYH9-USP6 fusion in the two hip cases and a COL1A1-USP6 fusion in the shoulder case."

33404853

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"A molecular analysis performed on the FNAB sample confirmed the presence of COL1A1::USP6 fusion, which is considered diagnostic for MO in the appropriate clinical context."

40260834

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"Thirteen cases showed COL1A1::USP6 fusion, one showed MYH9::USP6 fusion, and 4 were negative for common fusion types."

36727055

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"The reaction was performed at 37°C for 60 minutes, heated for 10 minutes at 65°C, and then kept at 4°C. A one-step polymerase chain reaction (PCR) was performed for amplification of the COL1A1–USP6 fu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

18068538

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"To verify the presence of a COL1A1–USP6 fusion transcript, the 330-bp fragment was analyzed by direct sequencing, which showed that nucleotide 222 of COL1A (NM_000088) was fused with nucleotide 1696 o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

18068538

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"Pathology revealed the presence of muscular tissue mixed with fibroblastic/myofibroblastic proliferation and ossification areas consistent with myositis ossificans (Fig. xref ); COL1A1-USP6 fusion transcript upon molecular investigation by RT-PCR method was found."

35434525

USP6 affects ARF6

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USP6 binds ARF6.

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USP6 binds ARF6. 10 / 15

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"Via its TRE-2/Bub2/CDC16 (TBC) domain, TRE17 preferentially interacts with ARF6-GDP at tubular endosomes and facilitates its recycling to the PM ( xref )."

30042195

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"It has been found that the TBC domain of TRE17 binds Arf6-GDP ( xref )."

17145964

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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]."

| PMC

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"Collectively, these results indicate that, unlike the TBC domain of TRE17 , which preferentially binds Arf6-GDP ( xref ), the TBC domain of EPI64 specifically binds Arf6-GTP."

17145964

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"Based on our observation of internalization of CD147 prior to TRE17-mediated trafficking ( xref ) and the preferential binding of TRE17 to ARF6-GDP ( xref ), the former is more likely, as ARF6 undergoes GTP hydrolysis at SEs via interaction with the ACAP1/2 GAPs ( xref )."

30042195

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"TRE17 associates directly with Arf6 in its GDP- but not GTP-bound state."

15509780

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"An interaction between USP6 and Arf6 was identified with a role of USP6 in Arf6 activation by promoting its recruitment to the plasma membrane."

17961905

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"Later on, it was found that TBC domain of USP6 interacts with Arf6, a GTPase member of the Arf family, rather than a Rab."

40348771

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"Second, it was recently reported that the TBC domain of TRE17 binds to Arf6-GDP ( xref )."

17145964

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"TRE17 binding to ARF6 increases its activation ; although TRE17 does not itself have GEF activity towards ARF6, it may facilitate interaction of ARF6 with another GEF."

21587297

USP6 binds EPI64 and ARF6. 1 / 1

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"Collectively, these results indicate that, unlike the TBC domain of TRE17 , which preferentially binds Arf6-GDP ( xref ), the TBC domain of EPI64 specifically binds Arf6-GTP."

17145964

USP6 activates ARF6.

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USP6 activates ARF6. 2 / 3

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"USP6 promotes plasma membrane localization of ARF6, and selectively regulates ARF6-dependent endocytic protein trafficking [ 5 ]."

30297112

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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]."

| PMC

ARF6 affects USP6

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ARF6 binds USP6.

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USP6 binds ARF6. 10 / 15

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"Via its TRE-2/Bub2/CDC16 (TBC) domain, TRE17 preferentially interacts with ARF6-GDP at tubular endosomes and facilitates its recycling to the PM ( xref )."

30042195

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"It has been found that the TBC domain of TRE17 binds Arf6-GDP ( xref )."

17145964

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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]."

| PMC

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"Collectively, these results indicate that, unlike the TBC domain of TRE17 , which preferentially binds Arf6-GDP ( xref ), the TBC domain of EPI64 specifically binds Arf6-GTP."

17145964

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30042195

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"TRE17 associates directly with Arf6 in its GDP- but not GTP-bound state."

15509780

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"An interaction between USP6 and Arf6 was identified with a role of USP6 in Arf6 activation by promoting its recruitment to the plasma membrane."

17961905

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"Later on, it was found that TBC domain of USP6 interacts with Arf6, a GTPase member of the Arf family, rather than a Rab."

40348771

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"Second, it was recently reported that the TBC domain of TRE17 binds to Arf6-GDP ( xref )."

17145964

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"TRE17 binding to ARF6 increases its activation ; although TRE17 does not itself have GEF activity towards ARF6, it may facilitate interaction of ARF6 with another GEF."

21587297

USP6 binds EPI64 and ARF6. 1 / 1

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"Collectively, these results indicate that, unlike the TBC domain of TRE17 , which preferentially binds Arf6-GDP ( xref ), the TBC domain of EPI64 specifically binds Arf6-GTP."

17145964

ARF6 activates USP6.

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ARF6 activates USP6. 1 / 1

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"Rueckert's study [35] argues that Arf6/ALAP1 protein activates the TBC (Tre-2/Cdz 16/Bub 2) protein domain USP6 (also called TRE17) to promote cell proliferation and migration."

28625359

USP6 affects GOLPH3

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USP6 binds GOLPH3.

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USP6 binds GOLPH3. 10 / 10

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"Through mechanical binding, circCYFIP2 enhances the interaction between GOLPH3 and USP6, inducing DDP resistance both in vitro and in vivo.To sum up, USP6 functions as a deubiquitinase that targets and increases the stability of the GOLPH3 protein in COAD."

40348771

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"Notably, circCFYIP2 interacted with both GOLPH3 and USP6 protein, and facilitated GOLPH3 deubiquitination through an intensified binding of USP6 to GOLPH3, which resulted in platinum resistance in COA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38735445

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"Therefore, CoIP assay was performed to confirm the direct interaction between USP6 and GOLPH3."

38735445

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"As shown in Fig. 2 A, Flag-tagged GOLPH3 was able to pulldown HA-tagged USP6 and vice-versa in HEK293T cells, indicating that USP6 interacts with GOLPH3."

38735445

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"Interestingly, after GOLPH3 was IP from HEK293T cells with circCYFIP2 silence, the following USP6 level was downregulated ( Fig. 10 D), which revealed that circCYFIP2 knockdown significantly hindered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38735445

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"Through mechanical binding, circCYFIP2 enhances the interaction between GOLPH3 and USP6, inducing DDP resistance both in vitro and in vivo."

40348771

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"CircCFYIP2 was found to directly interact with USP6 and GOLPH3 protein, thereby strengthening the deubiquitination process of GOLPH3 mediated by USP6, which ultimately enhanced GOLPH3 stability and pr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38735445

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38735445

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"Therefore, CoIP assay was performed to confirm the direct interaction between USP6 and GOLPH3."

38735445

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38735445

USP6 deubiquitinates GOLPH3.

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USP6 deubiquitinates GOLPH3. 2 / 2

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"In this article, we affirmed that USP6 was directly responsible for the deubiquitination of GOLPH3 protein and acted as an oncoprotein in COAD."

38735445

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"By deubiquitinating GOLPH3, Overexpression of USP6 increased the viability of COAD cells, prevented apoptosis, and sped up the growth of transplanted tumors both in vivo and in vitro."

40348771

USP6 activates GOLPH3.

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USP6 activates GOLPH3. 2 / 2

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"It is verified that the CDH11-USP6 fusion transcript is a specific transcript of ABC, the oncogenic property of which is closely linked with the upregulated transcription of USP6 [ 185 ]."

36641861

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"Targeted RNA sequencing was performed and showed an USP6::CDH11 gene fusion, which is a highly specific and diagnostic gene fusion for ABC ( xref ) [ xref , xref ]."

38137051

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"The result of the CDH11–USP6 chimeric gene is that USP6 is transcriptionally upregulated."

18068538

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"We observed 25 gene fusions, namely 9 SS18::SSX1 , 8 EWSR1::FLI1 , 3 PAX3::FOXO1 , 2 EWSR1::WT1 , 1 EWSR1::NR4A3 , 1 HEY1::NCOA2 , and 1 CDH11::USP6 ( xref )."

40093980

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"CDH11-USP6 fusion is one of the most frequently identified genetic abnormalities (30% of cases) and additional mutations continue to be described [ xref ]."

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"CDH11-USP6 translocation is the most common, found in approximately one third of ABCs, while the frequency of other fusion partners is not known, due to the large number of fusion partners and small n[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30553465

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"PCR primers for RT-PCR evaluation of the CDH11-USP6 fusion oncogene were CDH11 +71F (5′-CGCCGCTGACTTGTGAAT-3′) and USP6 +1781R (5′-CTCGGTGTCCCTTGTCATACTT-3′)."

15509545

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"USP6 rearrangements exist in 65 to 70% of ABC cases and CDH11-USP6 fusion is present in an additional 30% of cases [ xref ]."

37522932

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"Of these, 10 cases (28%) exhibited rearrangement of both loci, and a fusion transcript CDH11-USP6 was confirmed by RT-PCR in each of these cases."

15509545

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"Furthermore, RT-PCR reactions corroborated these molecular cytogenetic results showing the presence of CDH11-USP6 fusion transcripts in these tumors."

15509545

USP6 affects RALBP1

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USP6 binds RALBP1. 10 / 15

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"Furthermore, IP assays showed that the binding of USP6 to RALBP1 decreased upon ALKBH5 overexpression (Fig. xref K)."

39815301

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"This inhibition prevents the formation of the RALBP1-USP6 complex, leading to increased degradation of RALBP1 and reduced activation of the downstream PI3K/Akt/mTOR pathway."

39815301

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"Collectively, our results indicated that WRAP53 promoted the binding of USP6 to RALBP1, thereby upregulating RALBP1 expression."

39815301

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"WRAP53 exerts a pro-cancer effect in GC, by acting as a scaffold that facilitates the physical interaction between USP6 and RALBP1 proteins, resulting in RALBP1 deubiquitylation and upregulation."

39815301

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"Co-IP assays using HA-tag RALBP1 and HA-tag USP6 overexpression vectors confirmed the endogenous RALBP1-USP6 protein complex (Fig. xref I , J)."

39815301

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"We speculated that WRAP53 facilitates the binding of USP6 to RALBP1, allowing USP6 to deubiquitinate RALBP1 and protect it from degradation."

39815301

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"The lower level of WRAP53 disrupts the interaction between USP6 and RALBP1 protein, promoting RALBP1 degradation and thereby suppressing the PI3K/Akt/mTOR signaling cascade, ultimately attenuating the progression of GC."

39815301

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"We speculated that WRAP53 facilitates the binding of USP6 to RALBP1, allowing USP6 to deubiquitinate RALBP1 and protect it from degradation."

39815301

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"Furthermore, IP assays showed that the binding of USP6 to RALBP1 decreased upon ALKBH5 overexpression (Fig. 6K)."

39815301

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"In this study, we show that the decrease in WRAP53 expression diminishes its function as a scaffold for the interaction between RALBP1 and USP6, resulting in increased degradation of RALBP1 and subsequently suppressing gastric cancer growth and metastasis."

39815301

Thraa affects USP6

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Thraa binds USP6. 10 / 12

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"Using specific antibody against TRα1 (designated as C4) in ChIP analysis, we found a strong binding of TRα1 to TRE2 in the bone marrow of euthyroid WT mice (bar 2 versus 1, Fig. xref )."

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"Using specific antibody against TRalpha1 (designated as C4) in ChIP analysis, we found a strong binding of TRalpha1 to TRE2 in the bone marrow of euthyroid WT mice (bar 2 versus 1, Fig."

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"As expected, a decreased binding of TRα1 to TRE2 was detected in the bone marrow of Thra1 PV /+as well in Thra1 PV /+ Ncor1 ΔID / ΔID mice (bars 6 and 8 versus bar 2, Fig. xref ) because anti-TRα1 antibody C4 cannot recognize TRα1PV."

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"Very low binding of NCOR1 to TRE2-bound TRα1 was detected in euthyroid WT mice."

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"Very low binding of NCOR1 to TRE2 bound TRalpha1 was detected in euthyroid WT mice."

29273766

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"Virtually no NCOR1 binding to TRE2 bound TRalpha1 was detected in Ncor1 DeltaID and DeltaID mice (bar 4 versus bar 2, Fig."

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"Virtually no NCOR1 binding to TRE2-bound TRα1 was detected in Ncor1 ΔID / ΔID mice (bar 4 versus bar 2, Fig. xref )."

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"However, significant binding of TRα1 to TRE2 was detected (compare bars 6 to 5, Fig. xref )."

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"In mice expressing NCOR1DeltaID, similar binding of TRalpha1 to TRE2 as in WT mice was found in the bone marrow of Ncor1 DeltaID and DeltaID mice (bar 4 versus bar 2)."

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"As expected, a decreased binding of TRalpha1 to TRE2 was detected in the bone marrow of Thra1 PV/+ as well in Thra1 PV/+ Ncor1 DeltaID and DeltaID mice (bars 6 and 8 versus bar 2, Fig."

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USP6 binds thraa and TRα1PV. 2 / 2

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"Using similar EMSA, we also found specific binding of TRα1 ( xref , lanes 5–9) and TRα1PV ( xref , lanes 11–15) to TRE2."

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"Similar significantly higher binding of TRα1 (bar 3 versus bar 1, xref ) and TRα1PV (bar 6 versus bar 2, xref ) to TRE2 ( CCCACG GAGAT TCCTGT , in the region -3699 to -3325 bp) were also detected."

28910278

USP6 affects CALM1

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USP6 binds CALM1. 10 / 14

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"Western blot results showed again that the expression level of the P6 protein was much lower in the leaves co-infiltrated with pUS-US71GFP, pCAM-USP6, and pCAM-FveIF3g compared with the control leaves ( xref D,E)."

30558257

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"We then examined the effect of FveIF3g on P6 trans-activating activity by co-infiltrating N. benthamiana leaves with pUS-US71GFP, pCAM-USP6, and pCAM-FveIF3g or pUS-US71GFP, pCAM-USP6, and pCAM-2300 (control)."

30558257

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"By 3 days post agro-infiltration (dpai), only the leaves co-infiltrated with pCAM-USP6 and pUS-US71GFP showed strong GFP fluorescence ( xref B)."

30558257

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"Western blot assays showed a high amount of the GFP protein had accumulated in the leaves co-infiltrated with pCAM-USP6 and pUS-US71GFP."

30558257

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"GFP fluorescence in the leaves co-infiltrated with pUS-US71GFP, pCAM-USP6, and pCAM-FveIF3g was much weaker than it was in the control leaves."

30558257

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"In contrast, a strong GFP fluorescence was observed in the pCAM-USP6 and US71GFP co-expressed leaves."

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"PCAM-USP6 was co-infiltrated with these three bicistronic constructs into N. benthamiana leaves."

30558257

➶

sparser

"Leaves co-infiltrated with pCAM-USP6 and an empty vector (pCAM-2300) were used as a negative control."

30558257

➶

sparser

"All of the leaves co-infiltrated with pUS-US71GFP and pCAM-USP6, p35S-Ca71GFP and pCAM-USP6, or pSY-SY71GFP and pCAM-USP6 showed strong GFP fluorescence under the UV illumination by 3 dpai."

30558257

➶

sparser

"Western blot assays showed that high levels of the P6 and the GFP proteins had accumulated in the leaves co-infiltrated with pCAM-USP6 and pUS-US71GFP, p35S-Ca71GFP, or pSY-SY71GFP."

30558257

USP6 affects JAK1

1 | 1 10 1

USP6 deubiquitinates JAK1.

| 1 4

USP6 deubiquitinates JAK1. 4 / 4

| 1 3

➶

reach

"USP6 works by directly deubiquitinating JAK1, which stabilizes and activates it."

40348771

➶

reach

"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."

27440725

➶

trips

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

27440725

➶

reach

"We discovered that USP6 was sufficient to directly induce the former two responses via deubiquitination and stabilization of Jak1, leading to phosphorylation and activation of STAT1 (20, 22, 23)."

37615015

Modified USP6 leads to the deubiquitination of JAK1. 1 / 1

| 1

➶

reach

"Co-expression of USP6, but not USP6 (short), completely abolished ubiquitination of Jak1 in vivo (XREF_FIG)."

27440725

USP6 activates JAK1.

| 3

USP6 activates JAK1. 3 / 3

| 3

➶

reach

"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."

27440725

➶

reach

27440725

➶

reach

"Jak1 is upregulated by USP6 in a USP dependent manner."

27440725

USP6 increases the amount of JAK1.

| 2

USP6 increases the amount of JAK1. 2 / 2

| 2

➶

reach

"RT-qPCR revealed that Jak1 mRNA levels were not increased by USP6 (XREF_SUPPLEMENTARY)."

| 4 8

➶

sparser

"TRE2 in vivo , we carried out ChIP assay on intestinal Analysis of the ChIP DNA by using a primer pair chromatin extracted from premetamorphic tadpoles flanking TRE2 showed that TR was bound to TRE2 in premetamorphic tadpole intestine and T3 treatment enhanced TR binding to TRE2 ( xref )."

31585895

➶

sparser

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

22800560

➶

reach

"TRE2 in vivo, we carried out ChIP assay on intestinal Analysis of the ChIP DNA by using a primer pair chromatin extracted from premetamorphic tadpoles flanking TRE2 showed that TR was bound to TRE2 in premetamorphic tadpole intestine and T3 treatment enhanced TR binding to TRE2 (Figure 5)."

31585895

➶

reach

"More importantly, TRE2 is bound by TR in the tadpole intestine and T3 treatment of premetamorphic tadpoles leads to increased level of the activation histone mark H3K79 methylation and recruitment of RNA polymerase II to the TRE2 in the tadpole intestine."

31585895

➶

sparser

"In any case, our findings together indicate that Dot1L gene is a direct T3 target gene that is regulated via binding of the TR predominantly to TRE2."

22800560

➶

reach

"To determine if the strong binding of TRE2 to the TR/RXR heterodimer was sequence-specific, we mutated the putative TRE2 at the positions known to be important for binding to TR/RXR heterodimer (Figure 3B) and determined the effect in the mobility shift assay."

31585895

➶

sparser

"On the other hand, as the DNA generated by sonication during the ChIP assay could be as long as 1 kb (typically averaging around 500 bp), we could not rule out the possibility that the signal observed at TRE1 was due to TR binding at TRE2."

22800560

➶

sparser

"This could occur if the TRE1 region was present in some large fragments of DNA immunoprecipitated due to TR binding to the TRE2."

22800560

➶

reach

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

22800560

➶

sparser

"As indicated above, given the limitation of the ChIP assay, it is possible that the weak TR ChIP signal at TRE1 was a result of TR binding at the TRE2 and TRE2 is the only TRE bound by TR during metamorphosis in the intestine and tail."

22800560

USP6 affects RELA

| 3 9

USP6 phosphorylates RELA.

| 2 8

USP6 leads to the phosphorylation of RELA. 6 / 6

| 2 4

➶

reach

"Phosphorylation of p65 is induced by USP6."

39507445

➶

reach

"Instead, USP6 promotes phosphorylation of p65 with the presence of both IKKα and IKKβ."

39507445

➶

sparser

"TRE17(long) induced phosphorylation of S536-p65 in both the MC3T3 stable cell lines and transiently transfected HeLa cells ( xref )."

22081069

➶

sparser

"TRE17(long) induced phosphorylation of S536-p65 in both the MC3T3 stable cell lines and transiently transfected HeLa cells ( xref )."

22081069

➶

sparser

"As seen in xref , TRE17-induced phosphorylation of p65 was significantly attenuated in cells depleted of each of the IKK subunits."

22081069

➶

sparser

"As seen in xref , TRE17-induced phosphorylation of p65 was significantly attenuated in cells depleted of each of the IKK subunits."

22081069

USP6 phosphorylates RELA on S536. 4 / 4

| 4

➶

sparser

"TRE17 stimulates phosphorylation of p65 at serine 536, a modification that has been associated with enhanced transcriptional activity and nuclear retention."

22081069

➶

sparser

"TRE17 stimulates phosphorylation of p65 at serine 536, a modification that has been associated with enhanced transcriptional activity and nuclear retention."

22081069

➶

sparser

"TRE17 induces phosphorylation of p65 on serine 536 through IKKα and IKKβ."

| 3 1

USP6 leads to the ubiquitination of GLS. 4 / 4

| 3 1

➶

reach

"Increased GLS1 ubiquitination caused by overexpression of USP6 reduced GLS protein."

38260856

➶

reach

"Overexpressing USP6 led to increased GLS1 ubiquitination and decreased GLS protein [52]."

40348771

➶

sparser

"Overexpressing USP6 significantly increased GLS1 ubiquitination to decrease GLS protein."

35091542

➶

reach

"Overexpressing USP6 significantly increased GLS1 ubiquitination to decrease GLS protein."

35091542

USP6 deubiquitinates GLS.

| 4

USP6 leads to the deubiquitination of GLS. 4 / 4

| 4

➶

reach

"Similarly, umbilical cord mesenchymal cell-derived exosomes were proven able to promote Imatinib-induced apoptosis in K562-R cells via miR-146a-5p and its target USP6, which suppress GLS1 ubiquitination, causing an increase in GLS protein (78)."

38260856

➶

reach

"Additionally, USP6 also inhibited GLS1 and CD147 ubiquitination, resulting in the inhibition of apoptosis and increased production of MMP."

38735445

➶

reach

"Studies have shown that USP6 suppresses GLS1 ubiquitination, resulting in an increase in GLS1 protein levels."

40348771

➶

reach

"Overexpression of USP6 reduces GLS1 ubiquitination, preventing breakdown and allowing for continued glutamine metabolism [52]."

40348771

USP6 binds GLS.

| 3

USP6 binds GLS. 3 / 3

| 3

➶

sparser

"USP6 interacted with GLS1 and inhibited GLS1 ubiquitination in CML cells."

35091542

➶

sparser

"Further studies showed that USP6 interacted with GLS1 and inhibited GLS1 ubiquitination in CML cells."

35091542

➶

sparser

"Together, these findings indicated that USP6 interacted with GLS1 and inhibited GLS1 ubiquitination."

35091542

USP6 inhibits GLS.

| 1

USP6 inhibits GLS. 1 / 1

| 1

➶

reach

"For example, in chronic myeloid leukemia, miR-146a-5p can target ubiquitin-specific protease 6 (USP6), which in turn affects the level of ubiquitination and hence degradation of GLS using K562-R cells [28]."

37009252

THR affects USP6

| 4 8

THR binds USP6. 10 / 12

| 4 8

➶

sparser

31585895

➶

sparser

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

22800560

➶

reach

"TRE2 in vivo, we carried out ChIP assay on intestinal Analysis of the ChIP DNA by using a primer pair chromatin extracted from premetamorphic tadpoles flanking TRE2 showed that TR was bound to TRE2 in premetamorphic tadpole intestine and T3 treatment enhanced TR binding to TRE2 (Figure 5)."

31585895

➶

reach

31585895

➶

sparser

"In any case, our findings together indicate that Dot1L gene is a direct T3 target gene that is regulated via binding of the TR predominantly to TRE2."

22800560

➶

reach

31585895

➶

sparser

22800560

➶

sparser

"This could occur if the TRE1 region was present in some large fragments of DNA immunoprecipitated due to TR binding to the TRE2."

22800560

➶

reach

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

22800560

➶

sparser

22800560

USP6 is modified

| 12

USP6 is methylated.

| 6

USP6 is methylated. 6 / 6

| 6

➶

sparser

"In contrast with observation from mammalian systems, arginine methylation of the budding yeast S. cerevisiae hnRNP-like proteins Npl3, Hrp1, and Nab2 promotes their proper nuclear export [ xref , xref ]."

22091396

➶

sparser

"However, Rmt1 is known to bind and/or methylate a number of proteins that process and export mRNA; methylation of Rmt1 target proteins Npl3, Hrp1, and Nab2 promotes their dissociation from nuclear factors and facilitates their export from the nucleus. xref – xref This is consistent with RPS2’s known functions of processing and exporting 20S rRNA, a precursor for 40s ribosomal subunits. xref , xref Our observation that RPS2 R10 dimethylation increases tenfold in stationary phase suggests that the cell may be facilitating export of RPS2 from the nucleus."

24486316

➶

sparser

"If methylated Nab2 and Hrp1 are part of a stable, cytoplasmic CLB2 messenger ribonucleoprotein particle (mRNP), this might suggest that interaction of CCR4-NOT with the CLB2 mRNP is not sufficient to [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

23706744

➶

sparser

"Consistent with our observation that different hnRNPs fail to accumulate in the cytoplasm when Hmt1 is inhibited, the lack of Nab2, Npl3, and Hrp1 methylation may prevent their binding to CLB2 mRNA."

23706744

➶

sparser

"Interestingly, methylated Hrp1 binds to the EE of mRNA with the same efficiency as its unmethylated counterpart, but the presence of RNA itself inhibits Hrp1 methylation, particularly if the RNA displays a strong binding affinity to Hrp1 [ xref ]."

39408571

➶

sparser

"Although methylation of hnRNPA1 had a slight effect on nonspecific binding to homopolymeric RNA (Rajpurohit et al., 1994) , methylation of yeast hnRNP Hrp1 did not affect its affinity for a specific [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

11461695

USP6 is phosphorylated.

| 3

USP6 is phosphorylated. 3 / 3

| 3

➶

sparser

"In addition to multiple reported methylation sites, a large number of Hrp1 phosphorylation sites have been identified [ xref , xref , xref , xref ]."

39408571

➶

| 9

USP6 activates Neoplasm Invasiveness. 7 / 7

| 7

➶

reach

"USP6 overexpression in colon cancer cell lines enhanced the invasion and aggregation of cancer cells in vitro and increased liver metastasis in vivo[72]."

38292842

➶

reach

"According to a recent study, USP6 also contributes to resistance to hormone treatment and chemotherapy by improving the invasion and migratory capacities of breast cancer."

40348771

➶

reach

"Furthermore, we demonstrate that inhibition of CD147 by a specific inhibitor alleviated the TRE17-promoted tumor cell invasion."

35926707

➶

reach

"However, the role of USP6 in the development of colon cancer has not been explored previously.Hence, in the present study, we discovered that 1) USP6 was highly expressed the in tumor tissues than tho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30297112

➶

reach

"In the present study, we demonstrated that high USP6 expression could promote the invasion of colon cancer cells in vitro and liver metastasis in nude mice."

30297112

➶

reach

"Suppression of USP6 expression inhibited the ability of colon cancer cells invasion and metastasis."

30297112

➶

reach

"Ubiquitin-specific protease TRE17/USP6 promotes tumor cell invasion through the regulation of glycoprotein CD147 intracellular trafficking."

35926707

USP6 activates Neoplasm Invasiveness. 2 / 2

| 2

➶

reach

"We previously reported that USP6 induces intratumoral infiltration and activation of multiple innate immune lineages in Ewing sarcoma xenografts in nude mice."

37615015

➶

reach

"USP6 induces intratumoral infiltration and activation of multiple innate immune lineages in xenografted nude mice."

37615015

USP6 inhibits Neoplasm Invasiveness.

| 1

USP6 inhibits Neoplasm Invasiveness. 1 / 1

| 1

➶

reach

35926707

GOLPH3 affects USP6

| 4 6

USP6 binds GOLPH3. 10 / 10

| 4 6

➶

reach

40348771

➶

reach

38735445

➶

sparser

"Therefore, CoIP assay was performed to confirm the direct interaction between USP6 and GOLPH3."

38735445

➶

sparser

"As shown in Fig. 2 A, Flag-tagged GOLPH3 was able to pulldown HA-tagged USP6 and vice-versa in HEK293T cells, indicating that USP6 interacts with GOLPH3."

38735445

➶

sparser

38735445

➶

sparser

"Through mechanical binding, circCYFIP2 enhances the interaction between GOLPH3 and USP6, inducing DDP resistance both in vitro and in vivo."

40348771

➶

sparser

38735445

➶

sparser

38735445

➶

reach

"Therefore, CoIP assay was performed to confirm the direct interaction between USP6 and GOLPH3."

38735445

➶

reach

38735445

USP6 affects Wnt

| 9

USP6 activates Wnt.

| 8

USP6 activates Wnt. 8 / 8

| 8

➶

reach

"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."

28064438

➶

reach

"USP6 enhances Wnt signaling by deubiquitylating Fzds, thereby increasing their cell-surface abundance."

27162353

➶

reach

"USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds."

27162353

➶

reach

"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]."

28913633

➶

reach

"USP6 promotes Wnt signaling by deubiquitylating Fzds, increasing their cell-surface presence."

40348771

➶

reach

"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."

34414184

➶

reach

36474192

➶

reach

"Additionally, the deubiquitinating enzymes UBPY and USP6 may promote the recycling of endocytosed FZD back to the surface and restore Wnt signaling."

29632210

USP6 decreases the amount of Wnt.

| 1

USP6 decreases the amount of Wnt. 1 / 1

| 1

➶

reach

"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."

34522027

USP6 affects SPARC

| 9

USP6 binds SPARC. 9 / 9

| 9

➶

sparser

"These three new cases included two new cases of Serpinh1-USP6 and one each of Col3A1-USP6, SPARC-USP6, and MYH9-USP6."

40348771

➶

sparser

"Patel et al. recently identified SPARC-USP6 translocation in a case of nodular fasciitis [13] ."

30553465

➶

sparser

"Another unusual fusion —SPARC::USP6 was detected in the case of girl in middle childhood with superficial nodular fasciitis of the temporal area."

36828621

➶

sparser

"These samples included different tumor types with different detected fusions and we have not identified a SPARC-USP6 fusion in any of these samples."

30553465

➶

sparser

"The breakpoints of fusion in our case are therefore newly identified breakpoints between SPARC and USP6, leading to the conclusion that this is a new type of SPARC-USP6 fusion."

30553465

➶

sparser

"In conclusion, we identified a novel SPARC-USP6 translocation in primary ABC, extending the list of known fusion partners."

30553465

➶

sparser

"Herein, we report a novel translocation, SPARC-USP6 , identified in a solid variant of primary ABC, by using NGS technology, thereby extending the list of known fusion partners."

30553465

➶

sparser

"Due to the possibility of degradation of RNA, two pairs of primers flanking the specific SPARC-USP6 fusion point were designed (Oligo Analyser 3.1, IDT Tools), based on fusion sequence identified by A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

30553465

➶

sparser

"Using the above criteria as threshold, in-frame fusion SPARC-USP6 was identified ( Fig. 2 , upper left)."

30553465

USP6 affects CTNNB1

| 1 2 6

USP6 binds CTNNB1.

| 5

USP6 binds CTNNB1. 5 / 5

| 5

➶

sparser

"The CTNNB1::USP6 gene fusion has not been previously reported in intraneural nodular fasciitis, although it has been reported in three entities including aneurysmal bone cyst, nodular fasciitis, and intravascular fasciitis."

35175167

➶

sparser

"Next-generation sequencing uncovered the presence of a CTNNB1::USP6 gene fusion involving CTNNB1 gene in exon 1 at the genomic position chr3:41241161 and the USP6 gene in exon 1 at the genomic position chr17:5033231."

35175167

➶

sparser

"Intraneural Nodular Fasciitis of the Femoral Nerve with A Unique CTNNB1::USP6 Gene Fusion: Apropos of a Case and Review of Literature."

35175167

➶

sparser

"Lu et al. [ xref ] reported a novel CTNNB1-USP6 fusion in IVF, showing that IVF is a USP6 -induced neoplasm and should be included in USP6 -rearranged lesions."

33775935

➶

sparser

"Correction to: Novel CTNNB1-USP6 fusion in intravascular fasciitis of the large vein identified by next-generation sequencing."

32472194

USP6 activates CTNNB1.

| 1 1 1

USP6 activates CTNNB1. 3 / 3

| 1 1 1

➶

reach

"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."

32998794

➶

sparser

33558334

➶

eidos

"In these models , activation of STAT3 , NF-kappaB , and beta-catenin by USP6 was essential for tumorigenesis , as genetic or pharmacologic inhibition of these pathways significantly attenuated xenograft growth ( 16 , 23 , 24 ) ."

33558334

USP6 decreases the amount of CTNNB1.

| 1

USP6 decreases the amount of CTNNB1. 1 / 1

| 1

➶

reach

34522027

SPARC affects USP6

| 9

USP6 binds SPARC. 9 / 9

| 9

➶

sparser

"These three new cases included two new cases of Serpinh1-USP6 and one each of Col3A1-USP6, SPARC-USP6, and MYH9-USP6."

40348771

➶

sparser

"Patel et al. recently identified SPARC-USP6 translocation in a case of nodular fasciitis [13] ."

30553465

➶

sparser

"Another unusual fusion —SPARC::USP6 was detected in the case of girl in middle childhood with superficial nodular fasciitis of the temporal area."

36828621

➶

sparser

"These samples included different tumor types with different detected fusions and we have not identified a SPARC-USP6 fusion in any of these samples."

30553465

➶

sparser

"The breakpoints of fusion in our case are therefore newly identified breakpoints between SPARC and USP6, leading to the conclusion that this is a new type of SPARC-USP6 fusion."

30553465

➶

sparser

"In conclusion, we identified a novel SPARC-USP6 translocation in primary ABC, extending the list of known fusion partners."

30553465

➶

sparser

"Herein, we report a novel translocation, SPARC-USP6 , identified in a solid variant of primary ABC, by using NGS technology, thereby extending the list of known fusion partners."

30553465

➶

sparser

30553465

➶

sparser

"Using the above criteria as threshold, in-frame fusion SPARC-USP6 was identified ( Fig. 2 , upper left)."

30553465

USP6 affects cell population proliferation

| 8

USP6 activates cell population proliferation.

| 7

USP6 activates cell population proliferation. 7 / 7

| 7

➶

reach

"The overactive USP6 protein promotes cell survival, proliferation, and resistance to apoptosis, all of which are significant features of cancer growth."

40348771

➶

reach

"In human CRC cell lines, USP6 knockdown reduced cell proliferation, caused G0/G1 cell cycle arrest, and stopped cells from becoming tumorigenic in nude mice."

40348771

➶

reach

"USP6 depletion could inhibit cell proliferation and migration, reduce the colony number and induce apoptosis, which could be reversed by GOLPH3 overexpression in HT29 and HCT116 cells ( Fig. 3 F–I)."

38735445

➶

reach

"Tre2 (USP6NL) promotes colorectal cancer cell proliferation via Wnt and beta-catenin pathway."

31015802

➶

reach

"The identification of the USP6 gene as a recurrent and specific finding in these studies has led to the conclusion that NF is a form of neoplastic proliferation [13–15]."

39930390

➶

reach

"Therefore, the upregulation of USP6 expression can enhance proliferation and hinder apoptosis by means of the GOLPH3 protein in COAD.USP6 rearrangements were initially discovered in a primary aneurysm[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38735445

➶

reach

"USP6 silencing suppressed the migration and proliferation in primary Schwann cells."

37702221

USP6 inhibits cell population proliferation.

| 1

USP6 inhibits cell population proliferation. 1 / 1

| 1

➶

reach

"The injection of USP6-overexpressing cells into nude mice initiates aneurysmal bone cyst (ABC)-like tumor development by inducing the production of matrix metalloproteinases following NF-kB activation[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

23933176

USP6 affects Interferon

| 6 2

USP6 activates Interferon.

| 5

USP6 activates Interferon. 5 / 5

| 5

➶

reach

"We previously reported that USP6 is sufficient to induce type I and type II IFN response gene signatures, which includes the immunostimulatory chemokines CXCL9 and CXCL10 (20)."

37615015

➶

reach

"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."

30131449

➶

reach

"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."

28505176

➶

| 4

USP6 inhibits apoptotic process. 4 / 4

| 4

➶

reach

"By deubiquitinating GOLPH3, Overexpression of USP6 increased the viability of COAD cells, prevented apoptosis, and sped up the growth of transplanted tumors both in vivo and in vitro."

40348771

➶

reach

"Silencing USP6 expression inhibited cell migration and promoted apoptosis in HCT-116 and HT29 cells."

38735445

➶

reach

"Leukemia cells’ apoptosis was dramatically reduced by USP6 overexpression in response to imatinib."

38260856

➶

reach

"Instead, upregulation of USP6 or GOLPH3 expression can effectively improve cell migration ability and inhibit apoptosis ( Fig. 3 C, 3D)."

38735445

USP6 activates apoptotic process.

| 3

USP6 activates apoptotic process. 3 / 3

| 3

➶

reach

38735445

➶

reach

"The overactive USP6 protein promotes cell survival, proliferation, and resistance to apoptosis, all of which are significant features of cancer growth."

40348771

➶

reach

"USP6 also induces surface upregulation of the receptor for the apoptosis-inducing ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), providing an additional route for enhanced sensitivity to NK cell killing."

37615015

USP6 affects TRE1

| 4 3

TRE1 binds USP6. 7 / 7

| 4 3

➶

sparser

"Spin quantitation of the raw EPR spectra indicates 28% and 20% of Fp TRE1 and Fp TRE2 monomers, respectively, harbor a radical."

39392720

➶

reach

"In insects, two forms of Tre were found by protein purification and enzyme activity determination: soluble trehalase (Tre1) and membrane-bound trehalase (Tre2)."

36421713

➶

reach

"To date, insect trehalase has been shown to exist in two distinct forms, the soluble form Tre1 and the membrane-bound form Tre2."

37666623

➶

reach

"However, no significant alteration in glucose content in the hemolymph was found in between fenoxycarb-treated group and control during processing.After treated with two IGRs (0.1 mg/g) for 144 h, the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

31973871

➶

reach

"In insects, two distinct TREs have been characterized so far: soluble trehalase (TRE1) and membrane-bound trehalase (TRE2) (Shukla et al., 2015; Xu et al., 2022), which cooperate with each other to maintain energy supply in insects."

39399419

➶

sparser

"Taken together, these results suggest that TR/RXR binds independently to both TRE1 and TRE2."

16899449

➶

sparser

"ASH1 turned out to possess a surprising specificity in that it binds in vitro sense tre1 , tre2 and tre3 RNAs, but not the antisense counterparts."

16732899

USP6 affects GRIN

| 4 3

USP6 binds GRIN.

| 3

USP6 binds GRIN. 2 / 2

| 2

➶

sparser

"After establishing a role for USP6 in modulating NMDAR ubiquitination and expression, we determined whether USP6 interacts with NMDAR subunits."

31841517

➶

sparser

"Together, these results indicate that USP6 can interact with NMDAR subunits and promotes their stabilization by reducing NMDAR ubiquitination."

31841517

HMBS binds GRIN, USP6, and NMDAR. 1 / 1

| 1

➶

sparser

"USP6 interacts with NMDARs to attenuate UPS-mediated NMDAR turnover."

31841517

USP6 activates GRIN.

| 2

USP6 activates GRIN. 2 / 2

| 2

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reach

"The findings suggest that USP6 promotes synaptic function and cognition by stabilizing NMDAR [78]."

| 2 5

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"The overactive USP6 protein promotes cell survival, proliferation, and resistance to apoptosis, all of which are significant features of cancer growth."

40348771

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eidos

"In contrast , absence of USP6 caused a significant decrease in cell survival versus NT control siRNA cells after high-LET alpha - particle irradiation ( Fig. 2B , 2D ) and high-LET protons ( Fig. 2F , 2H ) ."

30851349

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"Conversely, overexpression of USP6 or GOLPH3 caused a notably higher cell viability in colon cancer cells than the LV-vector group, with a significant increase in colony numbers ( Fig. 3 A, B)."

38735445

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"Jak1 is required for STAT3 activation by USP6, and both are required for USP6 mediated cell survival and tumorigenesis."

27440725

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"Using high-LET protons (Fig. 1C; Fig. E1B, available online at https://doi.org/10.1016/j.ijrobp.2019.02.053), depletion of USP6 (plus CYLD, USP7, USP31, and USP9X) also reduced cell survival by >40%."

30851349

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reach

"Depletion of USP6 decreased cell survival specifically after high-LET alpha-particles and protons, but not low-LET protons or x-rays."

30851349

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eidos

"This approach identified ubiquitin specific protease 6 ( USP6 ) , which modulates cell survival after high-LET IR by promoting efficient repair of CDD sites ."

30851349

TRE1 affects USP6

| 4 3

TRE1 binds USP6. 7 / 7

| 4 3

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"Spin quantitation of the raw EPR spectra indicates 28% and 20% of Fp TRE1 and Fp TRE2 monomers, respectively, harbor a radical."

39392720

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"In insects, two forms of Tre were found by protein purification and enzyme activity determination: soluble trehalase (Tre1) and membrane-bound trehalase (Tre2)."

36421713

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reach

"To date, insect trehalase has been shown to exist in two distinct forms, the soluble form Tre1 and the membrane-bound form Tre2."

37666623

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31973871

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39399419

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"Taken together, these results suggest that TR/RXR binds independently to both TRE1 and TRE2."

16899449

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"ASH1 turned out to possess a surprising specificity in that it binds in vitro sense tre1 , tre2 and tre3 RNAs, but not the antisense counterparts."

16732899

USP6 affects TREH

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TREH binds USP6. 6 / 6

| 6

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31973871

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"The first enzyme involved in chitin synthesis is TRE ( Fig. 2 ), which occurs in two forms, soluble TRE (TRE1) and membrane-bound TRE (TRE2)."

30902530

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"In insects, two forms of Tre were found by protein purification and enzyme activity determination: soluble trehalase (Tre1) and membrane-bound trehalase (Tre2)."

36421713

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reach

"Two distinct forms of Tre exist in insects, soluble Tre (Tre1) and membrane-bound Tre (Tre2)."

38535338

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reach

39399419

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reach

"Trehalase is divided into soluble (TRE1) and membrane-bound trehalase (TRE2), and is a glycosidase that is responsible for hydrolyzing trehalose into two glucose molecules (Tang et al., 2017; Tang et al., 2018)."

37064912

USP6 affects Sarcoma, Ewing

| 6

USP6 inhibits Sarcoma, Ewing.

| 4

USP6 inhibits Sarcoma, Ewing. 4 / 4

| 4

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37615015

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"Here we report that natural killer (NK) cells are essential for its tumor-inhibitory functions, as NK cell depletion reverses USP6-mediated suppression of Ewing sarcoma xenograft growth."

37615015

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reach

"NK Cells are Required for Suppression of Ewing Sarcoma Tumor Growth by USP6."

37615015

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reach

"We previously demonstrated that USP6 inhibits growth of Ewing sarcoma tumors when xenografted into nude mice, but not NSG mice (20)."

37615015

USP6 activates Sarcoma, Ewing.

| 2

USP6 activates Sarcoma, Ewing. 2 / 2

| 2

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"Furthermore, in cocultured primary mouse LAKs and Ewing sarcoma cells, USP6 promotes LAKs maturation (from CD27 CD11bl to CD27 CD11b )."

37615015

➶

reach

"Our study provides further insight into the mechanism by which USP6 modulates the immune TME in Ewing sarcoma to suppress tumorigenesis."

37615015

USP6 affects MYL2

3 1 | 1 1

USP6 binds MYL2. 2 / 6

3 1 | 1 1

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"Although the biological significance of these interactions remains unknown, the observation that USP6 appeared to cause redistribution of Myl2 and LOC91526 to the cell membrane lead to the proposal that the binding of USP6 to Myl2 participates in RhoGTPase signaling [ xref , xref ]."

18687060

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18687060

USP6 affects Chemokine

| 4 2

USP6 activates Chemokine.

| 4

USP6 activates Chemokine. 4 / 4

| 4

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eidos

"USP6 synergistically enhances chemokine induction upon IFN treatment in vitro We previously reported that USP6 not only induces an IFN gene signature by itself , but that it also magnifies the response to exogenous Type I and II IFNs ( 17 ) ."

33558334

➶

eidos

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

33558334

➶

eidos

"Among the genes with the greatest synergistic induction were ligands for CXCR3 and CCR5 : USP6 or IFNalpha individually led to modest increases in levels of these chemokines , whereas expression was increased 2-4 orders of magnitude in USP6-expressing cells treated with IFNalpha ( Supplemental Figure 3B ) ."

| 6

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31973871

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reach

"The first enzyme involved in chitin synthesis is TRE ( Fig. 2 ), which occurs in two forms, soluble TRE (TRE1) and membrane-bound TRE (TRE2)."

30902530

➶

reach

"In insects, two forms of Tre were found by protein purification and enzyme activity determination: soluble trehalase (Tre1) and membrane-bound trehalase (Tre2)."

36421713

➶

reach

"Two distinct forms of Tre exist in insects, soluble Tre (Tre1) and membrane-bound Tre (Tre2)."

38535338

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reach

39399419

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reach

37064912

MYL2 affects USP6

3 1 | 1 1

USP6 binds MYL2. 2 / 6

3 1 | 1 1

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18687060

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18687060

USP6 affects TR/RXR

| 5

USP6 binds TR/RXR.

| 3

USP6 binds TR/RXR. 3 / 3

| 3

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"Thus, TR/RXR likely binds to TRE2 in the tadpole intestine and activates Sox3 gene transcription during metamorphosis when T3 is present."

27567710

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"In particular, one of them, TRE2 binds to TR/RXR heterodimers strongly in vitro and is required to mediate the activation of the Sox3 promoter by TR/RXR in the presence of T3 in reconstituted frog oocyte transcription system (XREF_FIG)."

27567710

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"Taken together, these results suggest that TR/RXR binds independently to both TRE1 and TRE2."

16899449

USP6 activates TR/RXR.

| 4 1

USP6 increases the amount of MMP9.

| 4

USP6 increases the amount of MMP9. 4 / 4

| 4

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"USP6 could initiate tumorigenesis and contribute to ABC pathogenesis by inducing the expression of MMP-9 and MMP-10 in the activity of USP-dependent manner [ 15 ]."

30297112

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reach

"Especially, USP6 induces the transcription of MMP9 through activation of NF-kappaB."

32904569

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

32904569

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reach

"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."

32904569

USP6 activates MMP9.

| 1

USP6 activates MMP9. 1 / 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."

20418905

USP6 affects JUN

3 | 1 1

USP6 binds JUN. 2 / 5

3 | 1 1

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"The interaction between USP6 and c-Jun contributes to the development of various tumors, including benign mesenchymal neoplasms like nodular fasciitis and aneurysmal bone cysts."

40348771

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"The interaction between USP6 and c-Jun contributes to the development of various tumors, including benign mesenchymal neoplasms like nodular fasciitis and aneurysmal bone cysts.One of the most striking features of USP6 in the context of cancer is its involvement in chromosomal translocations."

40348771

USP6 affects Carcinogenesis

| 5

USP6 activates Carcinogenesis.

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USP6 activates Carcinogenesis. 4 / 4

| 4

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"Mice allografts stably expressing USP6 and its vector demonstrate that USP6-mediated NF-κB upregulation promotes tumorigenesis and tumor vascularization (60)."

39507445

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reach

28449806

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reach

"USP6 has also been reported to initiate tumorigenesis via inducing the production of matrix metalloproteinases followed by NF-kappa-B activation [ 8 ]."

30297112

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reach

"The role of calcium with USP32 is undefined, but USP6 (97% sequence identity with USP32 as a chimeric fusion of USP32 and TBC1D3 ) induces tumorigenesis in a calcium-dependent manner through interaction with the ubiquitous calcium-binding protein calmodulin ."

35906355

USP6 inhibits Carcinogenesis.

| 1

USP6 inhibits Carcinogenesis. 1 / 1

| 1

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reach

"Our study provides further insight into the mechanism by which USP6 modulates the immune TME in Ewing sarcoma to suppress tumorigenesis."

37615015

USP6 affects CXCL10

| 2 3

USP6 activates CXCL10. 5 / 5

| 2 3

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"To further test this feedforward model, we sought to confirm whether CXCL9/CXCL10 were produced by the USP6/RD-ES cells, because NK cells are also capable of producing these chemokines (29, 34–36)."

37615015

➶

eidos

"As shown in Figure 2C , the first STAT1 site , both NF-kappaB sites , and the ISRE all contributed to activation of the CXCL10 promoter by USP6 + IFNgamma , whereas the AP-1 site was largely dispensable ."

33558334

➶

eidos

"This study demonstrates that high USP6 expression is associated with all of these hot TME hallmarks in ES patients , and that USP6 is sufficient to drive an IFN response signature and CXCL10 expression in vitro , as well as intra-tumoral immune cell recruitment and activation in vivo ."

33558334

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reach

37615015

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reach

"Upon activation, NK cells secrete IFNγ, which feeds back on USP6-expressing Ewing sarcoma cells to synergistically induce CXCL9/CXCL10."

37615015

USP6 affects BSG

| 4 1

USP6 activates BSG.

| 2

USP6 activates BSG. 2 / 2

| 2

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| 5

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"RNASeq further detected COL1A1-USP6 fusion in six cases and a novel ANGPTL2-USP6 fusion in one case."

32157177

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"A novel fusion ANGPTL2-USP6 is associated with distinct clinical and pathological presentation."

32157177

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sparser

"Case 3 had a novel ANGPTL2-USP6 fusion."

32157177

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sparser

"Case 3 was unique for the lack of zonal growth pattern and a novel ANGPTL2-USP6 fusion."

32157177

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"Aggressive fibromatosis-like tumour with ANGPTL2::USP6 fusion."

38379048

SS18 affects USP6

| 5

USP6 binds SS18. 5 / 5

| 5

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21536237

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"RT-PCR on the paraffin-embedded tumor for a potential SS18-USP6 translocation showed no evidence of a translocation."

21536237

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21536237

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22867995

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"Dual-color FISH also showed no evidence of a SS18-USP6 fusion."

21536237

REV affects USP6

| 5

USP6 binds REV. 5 / 5

| 5

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15793303

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"The cells stably co-infected with both pRev-TRE2 encoding for the C→S PTPμ mutant and pRev-Tet-Off were cultured in the presence and absence of 1 μg/ml of doxycycline."

15793303

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15793303

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"HMEC-1 cells were stably infected with either WT PTPμ, or the empty pRev-TRE2 vector, and cultured in the absence of doxycycline."

15793303

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15793303

PRMT2 affects USP6

| 3 2

PRMT2 methylates USP6. 4 / 4

| 2 2

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"Hmt1 methylates Yra1 and Hrp1, two mRNA binding proteins important for mRNA processing and export."

15314027

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sparser

"Hmt1 methylates Yra1 and Hrp1, two mRNA-binding proteins important for mRNA processing and export."

15314027

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sparser

"Taken together, these results suggest that methylation of Hrp1 and Nab2 by Hmt1 is required for interaction with the Ccr4-Not complex."

21464899

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reach

"Taken together, these results suggest that methylation of Hrp1 and Nab2 by Hmt1 is required for interaction with the Ccr4 and Not complex."

21464899

PRMT2 methylates USP6 on arginine. 1 / 1

| 1

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reach

"In S. cerevisiae , two RBPs involved in mRNA processing and export, Hrp1 and Yra1 (Aly/REF in metazoans), have been shown to be methylated by the major type I arginine methyltransferase, Hmt1 [42,43] [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

18342629

PAFAH1B1 affects USP6

| 5

USP6 binds PAFAH1B1. 5 / 5

| 5

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"Nanopore DNA Sequencing Detected Chromothripsis-Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma."

38979775

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sparser

"Subsequent next-generation sequencing-based technology revealed a novel PAFAH1B1-USP6 fusion gene as well as unusual fusion point on USP6 (exon 9)."

33161462

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sparser

"Additionally, PAFAH1B1-USP6 fusion has never been described in NF."

33161462

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sparser

"Atypical nodular fasciitis with a novel PAFAH1B1-USP6 fusion in a 22-month-old boy."

33161462

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"Retrospective nanopore DNA sequencing unexpectedly detected a PAFAH1B1::USP6 rearrangement."

38979775

NXF1 affects USP6

| 5

USP6 binds NXF1. 5 / 5

| 5

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37351636

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reach

37351636

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"Thus, it seems that defects in the cleavage reaction prevent binding between Hrp1 and Mex67, which would inhibit the nuclear export of the bound mRNA."

37351636

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reach

37351636

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reach

"Reassuringly, binding between Hrp1 and Mex67 was detected."

37351636

JUN affects USP6

➶

sparser

"Case 3 had a novel ANGPTL2-USP6 fusion."

32157177

➶

sparser

"Case 3 was unique for the lack of zonal growth pattern and a novel ANGPTL2-USP6 fusion."

32157177

➶

sparser

"Aggressive fibromatosis-like tumour with ANGPTL2::USP6 fusion."

38379048

USP6 affects natural killer cell activation

| 4

USP6 activates natural killer cell activation. 4 / 4

| 4

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"USP6 expression in Ewing sarcoma cells directly stimulates NK cell activation and degranulation in vitro, and functions by increasing surface levels of multiple NK cell-activating ligands."

37615015

➶

reach

"Given the robust NK cell activation and paracrine feedforward loop induced by USP6 intratumorally, we speculated that USP6 might trigger systemic immune activation in vivo."

37615015

➶

reach

"USP6 increases the surface levels of NK cell activation ligands, enhancing the interaction between NK cells and Ewing’s sarcoma cells, thus augmenting the tumor-killing capability of NK cells and highlighting the significance of USP6 in regulating the TME (Jain et al., 2023)."

38915446

➶

reach

"Expression of USP6 in Ewing sarcoma cells directly induces NK cell activation by driving surface upregulation of NK-activating ligands."

37615015

USP6 affects RNA14

| 4

USP6 binds RNA14. 4 / 4

| 4

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"Rna14 can further associate with Pcf11 and Hrp1 and also binds the Pfs2 and Cft1 subunits of CPF."

17151076

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reach

"The Hrp1/Rna14 interaction has been mapped to Hrp1 RRMs by NMR (Barnwal et al, 2012), but the structural details remain unknown."

35022249

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reach

37351636

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reach

"Interestingly, and in contrast to Hrp1, when we performed a similar RIP experiment with Rna14, we found an over ∼50% decrease in its association with the target mRNAs (Figure 5G, H), supporting a model in which Rna14 binding to Hrp1 might be the trigger of the Mex67 recruitment and suggesting Rna14 to function as an indicator of correct cleavage."

37351636

USP6 affects PPP6R3

| 4

USP6 binds PPP6R3. 4 / 4

| 4

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"In the literature, we encountered two cases with malignant clinical course. xref , xref In contrast to our case, both showed classical histologic features of NF and a PPP6R3–USP6 fusion with additional amplification suggesting that this specific amplified fusion gene is causative for the aggressive clinical course of the disease."

33625261

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"For example, a PPP6R3-USP6 fusion gene with amplification has been observed in rare cases of malignant NF, suggesting that this genetic alteration may confer malignant potential."

39445266

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sparser

"In the literature there are two cases reported with a PPP6R3::USP6 fusion and typical morphology of a nodular fasciitis but with a malignant transformation [ xref , xref ] ."

37951844

➶

sparser

"Both cases harbored a PP6R3::USP6 fusion and intriguingly amplification of the fused allele xref – xref ."

37150655

USP6 affects DNA-templated transcription

| 3 1

USP6 activates DNA-templated transcription.

| 2 1

USP6 activates DNA-templated transcription. 3 / 3

| 2 1

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"TRα1/T3 via interacting with TRE1 mediated suppression of the transcription whereas TRα1/T3 via interacting with TRE2 activated transcription."

28910278

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reach

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

28910278

➶

reach

"Thus, the intronic TRE2 can mediate transcription regulation by liganded TR/RXR in vivo."

31585895

USP6 inhibits DNA-templated transcription.

| 1

USP6 inhibits DNA-templated transcription. 1 / 1

| 1

➶

reach

"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]."

23870137

USP6 affects COL6A2

| 4

USP6 binds COL6A2. 4 / 4

| 4

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"For example, the COL6A2-USP6 fusion that was initially missed by RNA-seq because of low fusion fragments per million (< 0.1) combined with the absence of COL6A2 or USP6 on the inclusion list. (4) Finally, RNA-seq has a longer turnaround time of 7-21 days compared with more targeted approaches."

35085008

➶

sparser

"USP6 rearrangement with a COL6A2–USP6 fusion, DNA clustering analysis, and methylation profiling, however, led to the diagnosis of NF ( xref to xref )."

33625261

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sparser

"In case PMABM000BJK/27, a COL6A2-USP6 fusion was identified in routine diagnostics by targeted RNA-seq (Archer FusionPlex Sarcoma, Invitae, Boulder, CO) but not identified using RNA-seq."

35085008

➶

sparser

"We identified for NF known COL6A2–USP6 fusion. xref Also, methylation profiling and DNA-clustering analysis were consistent with NF."

33625261

USP6 affects CALM

| 1 3

CALM binds USP6. 4 / 4

| 1 3

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reach

"Calmodulin directly interacts with USP6 in a Ca 2+ -dependent pattern (i.e. this binding is regulated by physiological alteration in the level of Ca 2+ in vitro as well as in vivo)."

28659380

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sparser

"Point mutations within these motifs significantly reduced the interaction of TRE17 with CaM."

16127172

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sparser

"Calmodulin directly interacts with USP6 in a Ca 2+ -dependent pattern (i.e. this binding is regulated by physiological alteration in the level of Ca 2+ in vitro as well as in vivo )."

28659380

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sparser

"CaM bound directly to TRE17 in a Ca2+-dependent manner both in vitro and in vivo."

16127172

RNA14 affects USP6

| 4

USP6 binds RNA14. 4 / 4

| 4

➶

reach

"Rna14 can further associate with Pcf11 and Hrp1 and also binds the Pfs2 and Cft1 subunits of CPF."

17151076

➶

reach

"The Hrp1/Rna14 interaction has been mapped to Hrp1 RRMs by NMR (Barnwal et al, 2012), but the structural details remain unknown."

35022249

➶

reach

37351636

➶

reach

37351636

PPP6R3 affects USP6

| 4

USP6 binds PPP6R3. 4 / 4

| 4

➶

sparser

33625261

➶

sparser

"For example, a PPP6R3-USP6 fusion gene with amplification has been observed in rare cases of malignant NF, suggesting that this genetic alteration may confer malignant potential."

39445266

➶

sparser

"In the literature there are two cases reported with a PPP6R3::USP6 fusion and typical morphology of a nodular fasciitis but with a malignant transformation [ xref , xref ] ."

37951844

➶

| 4

➶

sparser

35085008

➶

sparser

"USP6 rearrangement with a COL6A2–USP6 fusion, DNA clustering analysis, and methylation profiling, however, led to the diagnosis of NF ( xref to xref )."

33625261

➶

sparser

"In case PMABM000BJK/27, a COL6A2-USP6 fusion was identified in routine diagnostics by targeted RNA-seq (Archer FusionPlex Sarcoma, Invitae, Boulder, CO) but not identified using RNA-seq."

35085008

➶

sparser

"We identified for NF known COL6A2–USP6 fusion. xref Also, methylation profiling and DNA-clustering analysis were consistent with NF."

33625261

CALM affects USP6

| 1 3

CALM binds USP6. 4 / 4

| 1 3

➶

reach

"Calmodulin directly interacts with USP6 in a Ca 2+ -dependent pattern (i.e. this binding is regulated by physiological alteration in the level of Ca 2+ in vitro as well as in vivo)."

28659380

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sparser

"Point mutations within these motifs significantly reduced the interaction of TRE17 with CaM."

16127172

➶

sparser

"Calmodulin directly interacts with USP6 in a Ca 2+ -dependent pattern (i.e. this binding is regulated by physiological alteration in the level of Ca 2+ in vitro as well as in vivo )."

28659380

➶

| 3

USP6 increases the amount of SMAD4.

| 2

USP6 increases the amount of SMAD4. 2 / 2

| 2

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"Overexpressing miR-130a or inhibiting USP6 in UM MUM-2B and MUM-2C cell lines reduced Wnt, β-catenin, and EGFR expression, activated SMAD4 expression, and reduced UM cell motility and invasion in vitro [21]."

40348771

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34522027

USP6 decreases the amount of SMAD4.

| 1

USP6 decreases the amount of SMAD4. 1 / 1

| 1

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reach

34522027

USP6 affects SKI

| 1 2

USP6 binds SKI.

| 2

USP6 binds SKI. 2 / 2

| 2

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"To determine whether the putative TRE2 in the first exon of the Ski gene can render TR/RXR-mediated T3 regulation of the promoter, we generated Ski promoter constructs containing either the wild type TRE2 (Ski-TRE2) or its mutant version (Ski-mTRE2), respectively, to drive firefly luciferase gene expression ( xref ) and evaluated T3-regulation of their activities in Xenopus oocytes ( xref )."

35944650

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"As shown in xref , the Ski-TRE2 promoter did not respond to T3 treatment in oocytes preinjected with GFP mRNA, but was strongly activated by T3 in oocytes preinjected with a mixture of TR/RXR mRNAs, suggesting that TRE2 mediated T3 induction through the binding of the TRE to TR/RXR."

35944650

USP6 increases the amount of SKI.

| 3

USP6 activates PLA1A.

| 2

USP6 activates PLA1A. 2 / 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]"

10882134

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reach

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

10882134

USP6 binds PLA1A.

| 1

PLA1A binds USP6. 1 / 1

| 1

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"In early studies in yeast, specific “downstream elements” (DSEs) were demonstrated to be important for triggering NMD and these DSEs were later shown to be bound by the RNA-binding protein Hrp1 that was critical for NMD for a subset of DSE-containing targets (Peltz et al. 1993; González et al. 2000)."

38198768

USP6 affects Neoplasm Metastasis

| 3

USP6 activates Neoplasm Metastasis. 3 / 3

| 3

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30297112

➶

reach

"Suppression of USP6 expression inhibited the ability of colon cancer cells invasion and metastasis."

30297112

➶

reach

"USP6 overexpression in colon cancer cell lines enhanced the invasion and aggregation of cancer cells in vitro and increased liver metastasis in vivo[72]."

38292842

USP6 affects MBD3

| 3

USP6 increases the amount of MBD3.

| 2

USP6 increases the amount of MBD3. 2 / 2

| 2

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| 2

USP6 increases the amount of GRIN1. 2 / 2

| 2

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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."

31841517

➶

reach

"In transfected cells, USP6 positively regulates GluN1 expression in neurons generated from human embryonic stem cells."

40348771

USP6 inhibits GRIN1.

| 1

USP6 inhibits GRIN1. 1 / 1

| 1

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reach

31841517

USP6 affects FZD

| 3

USP6 deubiquitinates FZD.

| 2

USP6 deubiquitinates FZD. 2 / 2

| 2

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"During the activation of Wnt signaling pathway, USP6 could increase Fzds cell-surface abundance and enhance Wnt by deubiquitylating Fzd [ 9 ]."

30297112

➶

reach

"Conversely, Fzd is deubiquitinated by USP6 and USP8 (Mukai et al. 2010; Jung et al. 2013; Madan et al. 2016)."

38383910

USP6 ubiquitinates FZD.

| 1 2

USP6 activates CXCL9.

| 2

USP6 activates CXCL9. 2 / 2

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37615015

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"Upon activation, NK cells secrete IFNγ, which feeds back on USP6-expressing Ewing sarcoma cells to synergistically induce CXCL9/CXCL10."

37615015

USP6 inhibits CXCL9.

| 1

USP6 inhibits CXCL9. 1 / 1

| 1

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eidos

"CRISPR deletion of Jak1 or STAT1 , but not STAT3 , dramatically suppressed the synergistic induction of CXCL10 and CXCL9 by USP6 + IFNgamma ( Figure 2A ) ( 17 ) ) ."

33558334

USP6 affects CENPA

| 3

USP6 increases the amount of CENPA.

sparser

"9 Furthermore, the TNC::USP6 fusion has also been documented in a primary aneurismal bone cyst."

36351867

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34520696

Translocation, Genetic affects USP6

| 3

Translocation, Genetic activates USP6.

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Translocation, Genetic activates USP6. 2 / 2

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"Notably, global DNA methylation analysis revealed that NOF and ABC presented distinct DNA methylation patterns, the latter being characterised by USP6 rearrangements caused by chromosomal translocations involving 17p13 locus [14]."

37555357

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reach

"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]."

28580205

Translocation, Genetic increases the amount of USP6.

| 1

Translocation, Genetic increases the amount of USP6. 1 / 1

| 1

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"In nodular fasciitis, chromosomal translocations cause overexpression of USP6, which activates the Wnt/β-catenin pathway [51]."

40348771

TRE affects USP6

| 3

TRE binds USP6. 3 / 3

| 3

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22982062

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"Thus, both TREs could bind to TR/RXR with TRE2 having a higher affinity in vitro."

22800560

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"Furthermore, both TREs were capable of binding to TR/RXR heterodimers in vitro with TRE2 having a higher affinity."

22800560

TR/RXR affects USP6

| 3

USP6 binds TR/RXR. 3 / 3

| 3

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"Thus, TR/RXR likely binds to TRE2 in the tadpole intestine and activates Sox3 gene transcription during metamorphosis when T3 is present."

27567710

➶

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27567710

➶

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"Taken together, these results suggest that TR/RXR binds independently to both TRE1 and TRE2."

16899449

PNA1 affects USP6

| 3

PNA1 binds USP6. 3 / 3

| 3

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"Next, we tested the binding of PNA1 to HRP1 at physiological pH (XREF_TABLE, entry 6)."

20527745

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| 2

USP6 binds Interferon. 2 / 2

| 2

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"We next explored whether USP6 was associated with an IFN response in other tumor types."

30131449

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"In addition, USP6 expression was associated with an IFN response in germ cell tumors."

30131449

Interferon activates USP6.

| 1

Interferon activates USP6. 1 / 1

| 1

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"Furthermore, USP6 renders Ewing sarcoma cells hyperresponsive to IFNs, such that IFN response genes are synergistically induced by ectopic IFNγ in Ewing sarcoma cells expressing USP6."

37615015

GRIN affects USP6

| 3

USP6 binds GRIN. 2 / 2

| 2

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sparser

"After establishing a role for USP6 in modulating NMDAR ubiquitination and expression, we determined whether USP6 interacts with NMDAR subunits."

31841517

➶

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"Together, these results indicate that USP6 can interact with NMDAR subunits and promotes their stabilization by reducing NMDAR ubiquitination."

sparser

28910278

MiR-145-5p affects USP6

| 1 1

MiR-145-5p inhibits USP6. 2 / 2

| 1 1

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"The study found that miR-145-5p suppressed USP6 by binding to its 3′UTR."

| 2

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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."

27162353

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36474192

USP9X affects PMS1

| 2

KRAS binds USP9X, KMT2D, PMS1, and USP6. 1 / 1

| 1

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"Interestingly, we found that mutations in KRAS , FAM46C, KMT2D, PMS1 and USP6 were significantly associated with drug resistance."

30809292

PMS1 binds USP6, SETD2, KMT2B, and USP9X. 1 / 1

| 1

| 2

USP6 activates response signature. 2 / 2

| 2

➶

eidos

33558334

➶

eidos

"We found that USP6 is sufficient to trigger an IFN response gene signature , both in ES cells and other neoplastic models ( 17 ) ."

33558334

USP6 affects regulation of cell cycle

| 2

USP6 inhibits regulation of cell cycle.

| 1

USP6 inhibits regulation of cell cycle. 1 / 1

| 1

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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."

30851349

USP6 activates regulation of cell cycle.

sparser

24575107

Hrp1 binds USP6. 1 / 1

| 1

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| 2

| 2

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"It is tempting to speculate that USP6’s ability to induce systemic immune activation and an abscopal response underlies the association of high USP6 expression with significantly improved overall survival of patients with Ewing sarcoma (20)."

37615015

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reach

"In 2011, Erickson-Johnson et al. observed that the MYH9 promoter region fused with the entire coding region of USP6, which resulted in overexpression of USP6 in NF [1]."

36741963

USP6 affects USP1

| 2

USP6 binds USP1. 2 / 2

| 2

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"Nevertheless, signal peptide prediction enabled identification of six genes encoding uncharacterized secretory proteins (USPs; USP1–USP6) that were commonly expressed in all examined social wasps, bumblebees, and one solitary hunting wasp, A. flavomarginatum ( xref )."

31947554

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"Properties of the Six USPs (USP1–USP6) as Putative Allergenic Proteins."

31947554

USP6 affects TRα1PV

| 2

| 1

| 1

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"Interestingly, we found that mutations in KRAS , FAM46C, KMT2D, PMS1 and USP6 were significantly associated with drug resistance."

30809292

PMS1 binds USP6, SETD2, KMT2B, and USP9X. 1 / 1

| 1

| 2

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"Using an enzyme-modified neutral comet assay after high-LET protons, we found that depletion of USP6 significantly reduces the efficiency of CDD repair (Fig. 4A [compare blue and yellow bars] and Fig. 4B), but not DSB repair, in comparison to NT control siRNA treated cells (Fig. 4A [compare green and red bars] and Fig. 4C)."

30851349

➶

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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."

30851349

USP6 affects NFASC

| 2

USP6 activates NFASC. 2 / 2

| 2

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"The driving mechanism by which the USP6 oncogenic fusion event produces the unique clinical behavior of NF is still poorly understood [14]."

38405650

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"Additionally, a positive finding of USP6 gene rearrangement with fluorescence in situ hybridization can further support the diagnosis of NF, which is a relatively recent method introduced [23]."

36824992

USP6 affects NAB2

| 2

USP6 binds NAB2. 2 / 2

| 2

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"Interestingly, a recent study showed that Hmt1p activity is required for Nab2 and Hrp1 binding to the CCR4-NOT complex ( Kerr et al., 2011 )."

23706744

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21464899

USP6 affects MMP10

| 2

USP6 increases the amount of MMP10. 2 / 2

| 2

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

32904569

➶

| 2

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"The Med15 and Hrp1 complex can associate with L-Mediator, and the subcomplex plays a role in the regulated transcription of some fission yeast genes."

28515143

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"Instead, Med15 forms a complex with Hrp1, a CHD1 ATP dependent chromatin remodeling protein."

reach

37615015

USP6 affects LUM

| 2

LUM binds USP6. 2 / 2

| 2

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"RNA sequencing detected LUM-USP6 and USP6-LUM fusion transcripts which were subsequently verified by RT-PCR/Sanger sequencing."

32859633

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"We report a novel t(12;17)(q21;p13) chromosome translocation which gave rise to a LUM-USP6 fusion in an aneurysmal bone cyst."

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32998794

USP6 affects KIF1A

| 2

USP6 binds KIF1A. 2 / 2

| 2

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"Eventually, the novel fusion KIF1A::USP6 was identified in the case of early adolescent male with superficial nodular fasciitis of the arm region."

36828621

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37615015

USP6 affects Hrp1p

| 2

USP6 inhibits Hrp1p. 2 / 2

| 2

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"A mutation in HRP1 that results in the stabilization of nonsense containing mRNAs abolishes the affinity of the Hrp1p for the DSE and fails to interact with Upf1p."

10882134

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"A mutation in HRP1 that resulted in the stabilization of nonsense containing mRNAs abolished the affinity of the Hrp1p for the DSE."

11674994

USP6 affects HTN3

| 2

USP6 binds HTN3. 2 / 2

| 2

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"For this purpose, we predicted the access energy [35] at the miR-302a*-target sequences using ParasoR [11] and constructed PB-TRE2.2MS-tagRFP-P2A-hmAG1(302a-5p)-Std1X, H2, and D4 vectors ( Supplementa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

28325684

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| 2

USP6 binds ABC transporters. 2 / 2

| 2

| 2

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"To demonstrate the binding of TRalpha1PV to TRE2, we used anti-TRalpha1PV specific antibodies, T1, in the ChIP assays."

29273766

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"In contrast, specific binding of TRalpha1PV to TRE2 was detected (compare bar 6 with bar 5), indicating that TRalpha1PV was bound to the promoter of the Gata1 gene."

29273766

TPM4 affects USP6

| 2

USP6 binds TPM4. 2 / 2

| 2

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"The first one represented old female in late 20s with deep nodular fasciitis of the proximal tibial region in which TPM4::USP6 fusion was proven."

36828621

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"Periosteal Fasciitis With Unusual Radiologic Features Harboring a Novel STAG1::USP6 Fusion Gene."

36694417

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"Molecular analysis revealed a novel STAG1::USP6 fusion that helped arrive at the right diagnosis and further expands the molecular profile of USP6 -associated neoplasms."

36694417

SREBF1 affects USP6

| 2

USP6 binds SREBF1. 2 / 2

| 2

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"Molecular testing revealed a novel SREBF1::USP6 fusion gene, confirming the final diagnosis of nodular fasciitis and ultimately expanding its molecular profile."

38304953

➶

sparser

"Palmer Nodular Fasciitis Harboring a Novel SREBF1::USP6 Fusion Gene."

38304953

SKI affects USP6

| 2

| 1

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sparser

"Interestingly, we found that mutations in KRAS , FAM46C, KMT2D, PMS1 and USP6 were significantly associated with drug resistance."

30809292

PMS1 binds USP6, SETD2, KMT2B, and USP9X. 1 / 1

| 1

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30809292

NAB2 affects USP6

| 2

| 1 1

USP6 binds JAK. 2 / 2

| 1 1

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"In vitro and in vivo, USP6 directly binds to and deubiquitinates JAK, protecting it from proteasomal destruction."

40348771

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| 2

USP6 binds HTN3. 2 / 2

| 2

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28325684

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"In addition, we constructed PB-TRE2.2MS-tagRFP-P2A-hmAG1(302a-5p)-Std2X, 3X, and 4X vectors, which contain multiple (2, 3, and 4) miR-302a* target sequences ( Supplementary Fig. S6a )."

28325684

GRIN1 affects USP6

| 2

GRIN1 ubiquitinates USP6. 1 / 1

| 1

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sparser

"USP6 transgenic mice had reduced GluN1 ubiquitination and depletion of USP6 in human embryonic stem cells differentiated into excitatory neurons resulted in a reduction in surface GluN1 leading to a model that the presence of USP6 stabilizes NMDA receptors perhaps through their recycling to the membrane ( xref )."

34197891

GRIN1 ubiquitinates USP6. 1 / 1

| 1

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34197891

EGFP affects USP6

| 2

KRAS binds EGFP and USP6. 2 / 2

| 2

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31208154

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33675800

EE affects USP6

| 2

USP6 binds EE. 2 / 2

| 2

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| 2

USP6 binds COL1A2. 2 / 2

| 2

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| 2

USP6 binds BUB2 and CDC16. 2 / 2

| 2

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16033705

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29233871

ABC transporters affects USP6

| 2

USP6 binds ABC transporters. 2 / 2

| 2

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"It has been said that ABC is associated with distinctive 17p13 translocations that result in up-regulation of USP6, a deubiquitinating enzyme.[ xref ]"

30809292

USP9X affects KRAS

| 1

KRAS binds USP9X, KMT2D, PMS1, and USP6. 1 / 1

| 1

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"Interestingly, we found that mutations in KRAS , FAM46C, KMT2D, PMS1 and USP6 were significantly associated with drug resistance."

30809292

USP9X affects KMT2B

| 1

| 1

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19955868

USP6 affects transcription antitermination

| 1

USP6 inhibits transcription antitermination. 1 / 1

| 1

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"Consistent with the direct interaction of CF factor Hrp1 with DEF1 attenuator RNA, mutations localized to a consensus pA site efficiency element (EE) and led to transcriptional readthrough that could be suppressed by HRP1 overexpression."

36315099

USP6 affects trans-aconitic acid

| 1

34335473

USP6 affects activation T cells

| 1

30809292

USP6 affects SACM1L

| 1

SACM1L binds USP6. 1 / 1

| 1

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"The pair-wise transcription regulatory interaction among the genes RCS1, a transcription factor involved in iron utilization and homeostasis, and GCN3, the alpha subunit of the translation initiation [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

19631244

USP6 affects RXR

| 1

30809292

USP6 affects Jak1 stabilization

| 1

USP6 activates Jak1 stabilization. 1 / 1

| 1

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eidos

"We envisage that USP6 engenders a potent positive feed-forward immunostimulatory loop as follows ( model , Figure 7B ) : USP6 directly induces Jak1 stabilization / STAT1 activation , leading to low level chemokine production , which we speculate stimulates recruitment of myeloid , NK , and T cells ; these factors may also enhance immune cell activation and proliferation ."

33558334

USP6 affects JAK-STAT

| 1

| 1

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37615015

USP6 affects IFNB

| 1

USP6 decreases the amount of IFNB. 1 / 1

| 1

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"To investigate the effect of USP6, we knocked down USP6 and USP8 in THP-1 cells and observed that USP6 knockdown slightly enhanced IFNB expression, while USP8 knockdown significantly decreased IFNB ex[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38795350

USP6 affects IFNAR1

| 1

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16458341

USP6 affects CD59

| 1

USP6 binds CD59, BSG, and EEA1. 1 / 1

| 1

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30809292

SACM1L affects USP6

| 1

SACM1L binds USP6. 1 / 1

| 1

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19631244

SA-miRNA gene affects USP6

| 1

SA-miRNA gene activates USP6. 1 / 1

| 1

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"Combinatorial regulation of SA-miRNA gene targets NAP1L1, SMARCD2 and USP6 by the miRNA from oncogenic MIR17HG and tumor-suppressive MIR100HG clusters."

28649425

RXR affects USP6

| 1

| 1

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30809292

PMS1 affects KRAS

| 1

KRAS binds USP9X, KMT2D, PMS1, and USP6. 1 / 1

| 1

| 1

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"Initial ctDNA analysis revealed presence of MYCN amplification, however a subsequent biopsy of the paraspinal tumor showed nodular fasciitis harboring a diagnostic PKM-USP6 fusion."

36108156

Neoplasms affects USP6

| 1

| 1

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30809292

Intellectual Disability affects USP6

| 1

| 1

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16458341

CEBPA affects USP6

| 1

CEBPA binds USP6. 1 / 1

| 1

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16458341

CD59 affects USP6

| 1

USP6 binds CD59, BSG, and EEA1. 1 / 1

| 1

| 1

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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."

22800560

IndraLab

Statements

USP6 affects MYH9

USP6 binds MYH9. 10 / 57

USP6 affects NFkappaB

USP6 activates NFkappaB. 10 / 31

USP6 affects Neoplasms

USP6 activates Neoplasms.

USP6 activates Neoplasms. 10 / 22

USP6 inhibits Neoplasms.

USP6 inhibits Neoplasms. 5 / 5

USP6 affects STAT3

USP6 activates STAT3.

USP6 activates STAT3. 10 / 19

USP6 phosphorylates STAT3.

USP6 phosphorylates STAT3. 3 / 3

USP6 affects COL1A1

USP6 binds COL1A1. 10 / 20

USP6 affects ARF6

USP6 binds ARF6.

USP6 binds ARF6. 10 / 15

USP6 binds EPI64 and ARF6. 1 / 1

USP6 activates ARF6.

USP6 activates ARF6. 2 / 3

ARF6 affects USP6

ARF6 binds USP6.

USP6 binds ARF6. 10 / 15

USP6 binds EPI64 and ARF6. 1 / 1

ARF6 activates USP6.

ARF6 activates USP6. 1 / 1

USP6 affects GOLPH3

USP6 binds GOLPH3.

USP6 binds GOLPH3. 10 / 10

USP6 deubiquitinates GOLPH3.

USP6 deubiquitinates GOLPH3. 2 / 2

USP6 activates GOLPH3.

USP6 activates GOLPH3. 2 / 2

USP6 increases the amount of GOLPH3.

USP6 increases the amount of GOLPH3. 1 / 1

USP6 decreases the amount of GOLPH3.

USP6 decreases the amount of GOLPH3. 1 / 1

USP6 affects CDH11

USP6 binds CDH11. 10 / 16

USP6 affects RALBP1

USP6 binds RALBP1. 10 / 15

Thraa affects USP6

Thraa binds USP6. 10 / 12

USP6 binds thraa and TRα1PV. 2 / 2

USP6 affects CALM1

USP6 binds CALM1. 10 / 14

USP6 affects JAK1

USP6 deubiquitinates JAK1.

USP6 deubiquitinates JAK1. 4 / 4

Modified USP6 leads to the deubiquitination of JAK1. 1 / 1

USP6 activates JAK1.

USP6 activates JAK1. 3 / 3

USP6 increases the amount of JAK1.

USP6 increases the amount of JAK1. 2 / 2

USP6 binds JAK1.

USP6 binds JAK1. 1 / 2

USP6 ubiquitinates JAK1.

Modified USP6 leads to the ubiquitination of JAK1. 1 / 1

USP6 affects THR

THR binds USP6. 10 / 12

USP6 affects RELA

USP6 phosphorylates RELA.

USP6 leads to the phosphorylation of RELA. 6 / 6

USP6 phosphorylates RELA on S536. 4 / 4

USP6 binds RELA.

RELA binds USP6 and IKK_complex. 1 / 1

USP6 activates RELA.

USP6 activates RELA. 1 / 1

USP6 affects GLS

USP6 ubiquitinates GLS.

USP6 leads to the ubiquitination of GLS. 4 / 4

USP6 deubiquitinates GLS.

USP6 leads to the deubiquitination of GLS. 4 / 4

USP6 binds GLS.

USP6 binds GLS. 3 / 3

USP6 inhibits GLS.