IndraLab
Statements
USP15 is modified
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USP15 is phosphorylated.
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rlimsp
"Although USP15 is predominantly cytoplasmic in interphase, we show that both isoforms move into the nucleus at prophase, but that isoform-1 is phosphorylated on its unique S229 residue at mitotic entry. The micronuclei phenotype we observe on USP15 depletion can be rescued by either USP15 isoform and requires USP15 catalytic activity. Importantly, however, an S229D phospho-mimetic mutant of USP15 isoform-1 cannot rescue either the micronuclei phenotype, or accumulation of TOP2A. Thus, S229 phosphorylation selectively abrogates this role of USP15 in maintaining genome integrity in an isoform-specific manner."
USP15 is ubiquitinated.
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USP15 is dephosphorylated.
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2
sparser
"As TRIM25 protein stability is regulated by the balance between degradative K48-linked ubiquitination and USP15-mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG-tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6-TRIM25-USP15 complex."
sparser
"It appeared that GLTSCR2 supported and inhibited the ability of USP15, respectively, to remove K63-linked and K48-linked ubiquitination of RIG-I. These results taken together indicated that GLTSCR2 interacted with RIG-I and USP15 in a complex to support the activity of USP15 to remove K63-linked polyubiquitin chains from RIG-I, leading to inactivation of RIG-I and blockage of IFN-β induction."
"USP15 specifically removed lysine 63-linked polyubiquitin chains from RIG-I among the essential components in RIG-I-like receptor-dependent pathway."
reach
"The overexpression of USP15-WT, but not of the deubiquitinase deficient mutants (USP15-C269A and USP15-H862A), significantly decreased the ubiquitination of RIG-I (XREF_FIG) and did not block ubiquitination of IPS-1 (XREF_FIG), TRAF3 (XREF_FIG) and TBK1 XREF_FIG), illustrating that USP15 has deubiquitination activity for RIG-I."
reach
"To the best of our knowledge, at least nine DUBs, A20, CYLD, USP3, USP5, USP14, USP15, USP21, USP25, and USP27X, have been proposed to counteract the K63linked ubiquitination of RIG-I and, thereby attenuate downstream signaling and IFN-b production ( Table 1 and Figure 3 ) (58, 76, 93) ."
reach
"Consistent with the negative regulatory role of USP15 in RIG-I-mediated signaling, USP15 substantially reduced RIG-I polyubiquitination in cells transfected with plasmid encoding the WT ubiquitin and Lys63 mutant (Fig. 5a,b), but not in the mutant-Lys48-transfected cells (Fig. 5c), indicating that USP15 has DUB activity directed specifically towards the Lys63-linked polyubiquitin chains of RIG-I."
reach
"Conversely, whereas USP4 and USP15 target p53 inhibiting ligases ARF-BP1 [XREF_BIBR] and MDM2 [XREF_BIBR], respectively, USP11 stabilizes p53 [XREF_BIBR] as well as several other tumor suppressors including PML [XREF_BIBR], BRCA2 [XREF_BIBR] and Mre11 complex members MRE11 & RAD50 [XREF_BIBR]."
sparser
"As TRIM25 protein stability is regulated by the balance between degradative K48-linked ubiquitination and USP15-mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG-tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6-TRIM25-USP15 complex."
reach
"These data indicate that Nef expressed from the wt-HIV-1-, but not from Deltanef-HIV-1-replicating cells, degraded USP15, lowering the amount of intracellular USP15, which in turn vitiated USP15 induced degradation of viral proteins and thereby HIV-1 replication, where Nef degrades USP15, but USP15 mediated Nef degradation is more potent (XREF_FIG)."
reach
"Further, while the amount of intracellular Nef and USP15 was mutually regulated, USP15 mediated degradation of Nef was stronger than Nef mediated USP15 degradation, implying that USP15 could be employed to knock out Nef, a molecule essential to pathogenicity, within HIV-1 infected cells."
reach
"Further, Nef, but not Gag, degraded USP15, suggesting that reciprocal degradation of Nef and USP15 could play a central role in coordinating decay of viral proteins and hence HIV-1 replication, underlining the dynamic competition between the molecular determinants of the infecting HIV-1 and the infected host cells."
reach
"These data indicate that Nef expressed from the wt-HIV-1-, but not from Deltanef-HIV-1-replicating cells, degraded USP15, lowering the amount of intracellular USP15, which in turn vitiated USP15 induced degradation of viral proteins and thereby HIV-1 replication, where Nef degrades USP15, but USP15 mediated Nef degradation is more potent (XREF_FIG)."
reach
"In this context, to achieve a certain biological outcome, the same DUB can regulate the pathway at different levels (e.g., USP15 and USP4 promote signaling by targeting the TGF-beta receptor and the effector SMADs) or multiple DUBs can act on the same target (e.g., USP15 and OTUB1 promote signaling through stabilizing R-SMADs)."
reach
"Conversely, whereas USP4 and USP15 target p53 inhibiting ligases ARF-BP1 [XREF_BIBR] and MDM2 [XREF_BIBR], respectively, USP11 stabilizes p53 [XREF_BIBR] as well as several other tumor suppressors including PML [XREF_BIBR], BRCA2 [XREF_BIBR] and Mre11 complex members MRE11 & RAD50 [XREF_BIBR]."
reach
"Furthermore, recent reports have identified a number of shared substrates of SMURF2 and USP15 including MDM2, SMAD3, and RNF20, suggesting that the association between SMURF2 and USP15 may serve as a common regulatory method to control multiple analogous cellular protein complexes XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR."
reach
"HEK293T cells were transfected with USP15-specific siRNAs or control siRNAs for 24 h. Cells were further infected with SEV or mock infected for 16 h before immunoblots with the indicated antibodies were performed.Figure 2: (a) USP15 inhibited the SEV-induced activation of the IFN-β promoter."
reach
"In conclusion, our results provide clear evidence that USP15 deconjugates the Lys63-linked polyubiquitin chains from RIG-I.Since the activation of RIG-I signaling requires Lys63-linked ubiquitination, then we investigated whether the overexpression of USP15, which removes the Lys63-linked polyubiquitin from RIG-I, will decreases the RIG-I-mediated activation of IFN-β promoter activity and the activation mediated by its constitutively active mutant, RIG-I-N."
sparser
"It appeared that GLTSCR2 supported and inhibited the ability of USP15, respectively, to remove K63-linked and K48-linked ubiquitination of RIG-I. These results taken together indicated that GLTSCR2 interacted with RIG-I and USP15 in a complex to support the activity of USP15 to remove K63-linked polyubiquitin chains from RIG-I, leading to inactivation of RIG-I and blockage of IFN-β induction."
reach
"As TRIM25 protein stability is regulated by the balance between degradative K48 linked ubiquitination and USP15 mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6, TRIM25, and USP15 complex."
sparser
"The Gaussia princeps luciferase protein complementation assay shows that USP15 interacts with the key oncoprotein human papillomavirus (HPV) E6, while USP29 and USP33 bind to E7 protein, suggesting that cellular DUBs impact HPV tumorigenesis by regulating the stability of the viral proteins [ xref ]."
sparser
"The Gaussia princeps luciferase protein complementation assay shows that USP15 interacts with the key oncoprotein human papillomavirus (HPV) E6, while USP29 and USP33 bind to E7 protein, suggesting that cellular DUBs impact HPV tumorigenesis by regulating the stability of the viral proteins [45]."
sparser
"In addition, putative mechanisms modulating E6-mediated degradation have been proposed, which include proteasome-mediated degradation of both E6 ( xref ) and E6AP ( xref ), stabilization of E6 by E6AP ( xref ), E6 interaction with the deubiquitinating enzyme USP15 ( xref ) and inhibition of the E6/E6AP activity by the EDD ubiquitin ligase ( xref )."
reach
"In addition, putative mechanisms modulating E6 mediated degradation have been proposed, which include proteasome mediated degradation of both E6 and E6AP, stabilization of E6 by E6AP, E6 interaction with the deubiquitinating enzyme USP15 and inhibition of the E6/E6AP activity by the EDD ubiquitin ligase."
sparser
"As TRIM25 protein stability is regulated by the balance between degradative K48-linked ubiquitination and USP15-mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG-tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6-TRIM25-USP15 complex."
reach
"Furthermore, recent reports have identified a number of shared substrates of SMURF2 and USP15 including MDM2, SMAD3, and RNF20, suggesting that the association between SMURF2 and USP15 may serve as a common regulatory method to control multiple analogous cellular protein complexes XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR."
USP15 affects cell population proliferation
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USP15 activates cell population proliferation.
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USP15 inhibits cell population proliferation.
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USP15 inhibits cell population proliferation. 2 / 2
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"In addition, USP15 overexpression reversed the inhibited proliferation and migration ability of glioma cells induced by GINS1 silencing in U251 cells, whereas USP15 knockdown impaired the elevated proliferation and migration ability of glioma cells induced by GINS1 overexpression in A72 cells."
USP15 affects apoptotic process
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USP15 inhibits apoptotic process.
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USP15 activates apoptotic process.
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"As TRIM25 protein stability is regulated by the balance between degradative K48 linked ubiquitination and USP15 mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6, TRIM25, and USP15 complex."
sparser
"The Gaussia princeps luciferase protein complementation assay shows that USP15 interacts with the key oncoprotein human papillomavirus (HPV) E6, while USP29 and USP33 bind to E7 protein, suggesting that cellular DUBs impact HPV tumorigenesis by regulating the stability of the viral proteins [ xref ]."
sparser
"The Gaussia princeps luciferase protein complementation assay shows that USP15 interacts with the key oncoprotein human papillomavirus (HPV) E6, while USP29 and USP33 bind to E7 protein, suggesting that cellular DUBs impact HPV tumorigenesis by regulating the stability of the viral proteins [45]."
sparser
"In addition, putative mechanisms modulating E6-mediated degradation have been proposed, which include proteasome-mediated degradation of both E6 ( xref ) and E6AP ( xref ), stabilization of E6 by E6AP ( xref ), E6 interaction with the deubiquitinating enzyme USP15 ( xref ) and inhibition of the E6/E6AP activity by the EDD ubiquitin ligase ( xref )."
reach
"In addition, putative mechanisms modulating E6 mediated degradation have been proposed, which include proteasome mediated degradation of both E6 and E6AP, stabilization of E6 by E6AP, E6 interaction with the deubiquitinating enzyme USP15 and inhibition of the E6/E6AP activity by the EDD ubiquitin ligase."
sparser
"As TRIM25 protein stability is regulated by the balance between degradative K48-linked ubiquitination and USP15-mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG-tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6-TRIM25-USP15 complex."
reach
"For example, the non structural protein 1 (NS1) of influenza A virus displaces the SPRY domain by binding to an overlapping contact site on the CC domain [XREF_BIBR], the V proteins of measles, Sendai and parainfluenza viruses bind to the SPRY domain and prevent the interaction of TRIM25 with RIG-I [XREF_BIBR], while the E6 proteins of oncogenic HPVs target TRIM25 and USP15 to promote degradation of the ligase [XREF_BIBR]."
USP15 affects Interferon
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USP15 inhibits Interferon.
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USP15 inhibits Interferon. 10 / 12
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"We will discuss them one by one.In a study using HEK293 T cells and Sendai virus (SeV), knockdown of the gene transcribing USP15 resulted in upregulation of type I IFN, while overexpression of USP15 decreased type I interferon as USP15 showed dose-dependent inhibition of IFN-β [16] ."
reach
"Although we can not rule out the possibility that USP15 exerts its effects in a third uncharacterized manner, the data in this study demonstrate that USP15 sequesters the interaction between RIG-I and IPS-1, shedding light on the mechanisms underlying the catalytic-activity-independent antagonism of IFN by USP15."
reach
"We will discuss the DUBs that influence the pathways of interferons (IFN), tumor necrosis factors (TNF), TNF-related apoptosis-inducing ligand (TRAIL), interleukins (IL) and chemokines.In a study using HEK293 T cells and Sendai virus (SeV), knockdown of the gene transcribing USP15 resulted in upregulation of type I IFN, while overexpression of USP15 decreased type I interferon as USP15 showed dose-dependent inhibition of IFN-β [16]."
USP15 activates Interferon.
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USP15 activates Interferon. 6 / 6
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reach
"In addition, we demonstrated that in contrast to USP15 de-ubiquitinating (DUB) activity, USP15 mediated inhibition of IFN signaling was not abolished by mutations eliminating the catalytic activity, indicating that a fraction of USP15 mediated IFN antagonism was independent of the DUB activity."
USP15 increases the amount of Interferon.
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"To determine whether there is a possible association between HBx and USP15, perhaps under more physiologic condition, the CytoTrap yeast two-hybrid system was employed, and the results demonstrated that HBx could interact with USP15, and the region between HBx amino acid residues 51 and 80 is required for the interaction with USP15."
sparser
"Given the observations that USP15 binds to HBx, trims ubiquitin from HBx, and consequently increases HBx stability and protein level, we went on to explore whether the transcriptional transactivation function of HBx could be increased as a result of elevated HBx protein level due to the interaction between USP15 and HBx."
sparser
"To determine whether there is a possible association between HBx and USP15, perhaps under more physiologic condition, the CytoTrap yeast two-hybrid system was employed, and the results demonstrated that HBx could interact with USP15, and the region between HBx amino acid residues 51 and 80 is required for the interaction with USP15."
reach
"Taken together these results demonstrate the mechanism by which USP15 leads to decreased Nrf2 protein levels : USP15 is able to stabilize the Cul3-Keap1-E3 ligase complex through deubiquitination of Keap1, resulting in increased E3 ligase activity and ubiquitination of Nrf2, which ultimately leads to degradation of the Nrf2 protein."
sparser
"To examine whether PRP31 interacts directly with USP15, glutathione beads immobilized with a GST-tagged DUSP-UBL domain of USP15 was incubated with PRP31, which was synthesized with the in vitro transcription/translation (IVT/T) in the absence or presence of the SART3 HAT domains."
reach
"To examine whether PRP31 interacts directly with USP15, glutathione beads immobilized with a GST tagged DUSP-UBL domain of USP15 was incubated with PRP31, which was synthesized with the in vitro transcription and translation (IVT/T) in the absence or presence of the SART3 HAT domains."
reach
"We found a novel protein protein interaction between ubiquitin specific protease 15 (USP15) and skeletal muscle LIM protein 1 (SLIM1) : USP15 and SLIM1 directly bound under cell-free conditions and co-immunoprecipitated from the lysates of the cells, where they were co-expressed; and USP15 deubiquitinated SLIM1, resulting in the increase of protein levels of SLIM1."
USP15 affects cell differentiation
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USP15 activates cell differentiation.
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USP15 inhibits cell differentiation.
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"In contrast, ectopic expression of USP15 did not augment TbetaRI levels or overall TGF-beta luciferase activity in SMURF2 CRSP1 cell lines when expressed alone or in combination with SMURF2 C/A indicating that USP15 's role in the TGF-beta pathway is dependent on SMURF2 function (XREF_SUPPLEMENTARY)."
sparser
"It appeared that GLTSCR2 supported and inhibited the ability of USP15, respectively, to remove K63-linked and K48-linked ubiquitination of RIG-I. These results taken together indicated that GLTSCR2 interacted with RIG-I and USP15 in a complex to support the activity of USP15 to remove K63-linked polyubiquitin chains from RIG-I, leading to inactivation of RIG-I and blockage of IFN-β induction."
reach
"Interestingly, we detected that reduction of endogenous GLTSCR2 resulted in increased USP15 activity in removing K48 linked ubiquitination of RIG-I-N in GLTSCR2 knockdown cells (XREF_FIG, lane 6), whereas GLTSCR2 presence reduced the activity of USP15 in removing K48 linked ubiquitination of RIG-I-N in HEK293T cells (lane 3)."
reach
"Interestingly, we detected that reduction of endogenous GLTSCR2 resulted in increased USP15 activity in removing K48-linked ubiquitination of RIG-I-N in GLTSCR2 knockdown cells (Fig. 6d, lane 6) , whereas GLTSCR2 presence reduced the activity of USP15 in removing K48-linked ubiquitination of RIG-I-N in HEK293T cells (lane 3)."
reach
"Interestingly, we detected that reduction of endogenous GLTSCR2 resulted in increased USP15 activity in removing K48-linked ubiquitination of RIG-I-N in GLTSCR2 knockdown cells (Fig. 6d, lane 6) , whereas GLTSCR2 presence reduced the activity of USP15 in removing K48-linked ubiquitination of RIG-I-N in HEK293T cells (lane 3)."
sparser
"Scale bar, 10 μm. (D) Quantification of the percentage of Parkin-positive cells (in the conditions transfected with Parkin and EV) or Parkin- and Myc-positive cells (in the conditions transfected with Parkin and USP15-Myc) in which Parkin colocalized with mitochondria (n = 3). (E) HEK293 cells were transfected with EV or Myc-tagged USP15 and treated with DMSO or CCCP (10 µm) for 3 h."
sparser
"Scale bar, 10 mm. (D) Quantification of the percentage of Parkin-positive cells (in the conditions transfected with Parkin and EV) or Parkin-and Myc-positive cells (in the conditions transfected with Parkin and USP15-Myc) in which Parkin colocalized with mitochondria (n ¼ 3). (E) HEK293 cells were transfected with EV or Myctagged USP15 and treated with DMSO or CCCP (10 mM) for 3 h."
sparser
"The negative regulation demonstrated in this study mediated by the USP15-CARD9 association could occur at multiple levels – deactivation of CARD9 after ubiquitination and modulation of CARD9-mediated signaling intensity, duration, or both – with the dynamic balance between TRIM62 and USP15 enzymatic activities likely critical in controlling the overall output of this pathway."
sparser
"Importantly, we observed that USP15 binds to CARD9 in BMDCs in the absence of stimulation and that this interaction is largely unaffected by Dectin-1 ligand binding, indicating that USP15 constitutively interacts with CARD9 and may act to prevent aberrant CARD9 signaling at steady state."
reach
"An in vitro ubiquitination assay revealed that IkappaBalpha ubiquitination was markedly inhibited by overexpression of CHMP5 or USP15 (XREF_FIG), which is accompanied with pulse-chase labeling experiments showing that IkappaBalpha stability was increased by overexpression of CHMP5 or USP15 (XREF_FIG)."
CGAS affects USP15
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sparser
"Although the direct interaction between cGAS and USP15 was abolished in the GST pull-down assay, their interaction remained to some extent after the IDR of USP15 was deleted in the co-IP assay, indicating the indirect interaction between cGAS and USP15 in cells, which might be responsible for the process of cGAS deubiquitylation by USP15 ( xref )."
reach
"Depletion of USP15 with two independent siRNA oligos does not interfere with this basic ubiquitylation ladder but promotes the appearance of an additional higher molecular weight ubiquitin smear above the 116-kDa marker that is indicative of the accumulation of distinct polyubiquitylated species of BRAP in the absence of USP15."
reach
"Both USP15 and USP4 stimulate TGF-beta signaling by deubiquitylating and stabilizing two key signaling molecules in this pathway, TGF-beta receptor I (TbetaRI) and R-SMADs, suggesting that these two closely related DUBs act in concert to modulate central signaling processes that are involved in oncogenesis and innate immunity."
sparser
"The negative regulation demonstrated in this study mediated by the USP15-CARD9 association could occur at multiple levels – deactivation of CARD9 after ubiquitination and modulation of CARD9-mediated signaling intensity, duration, or both – with the dynamic balance between TRIM62 and USP15 enzymatic activities likely critical in controlling the overall output of this pathway."
sparser
"Importantly, we observed that USP15 binds to CARD9 in BMDCs in the absence of stimulation and that this interaction is largely unaffected by Dectin-1 ligand binding, indicating that USP15 constitutively interacts with CARD9 and may act to prevent aberrant CARD9 signaling at steady state."
Mitoxantrone affects USP15
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Mitoxantrone inhibits USP15.
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Mitoxantrone binds USP15.
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"Since we have shown that USP15 is essential for maintaining HBx stability and that USP15 augments HBx mediated oncogenic signals, one inference from our work is that compromising USP15 might be a novel approach to abrogate cellular transformation and serve as a target for anti-cancer therapy."
USP15 increases the amount of X.
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USP15 affects Proteasome
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USP15 activates Proteasome.
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USP15 increases the amount of Proteasome.
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USP15 inhibits Proteasome.
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USP15 inhibits Proteasome. 1 / 2
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sparser
"Scale bar, 10 μm. (D) Quantification of the percentage of Parkin-positive cells (in the conditions transfected with Parkin and EV) or Parkin- and Myc-positive cells (in the conditions transfected with Parkin and USP15-Myc) in which Parkin colocalized with mitochondria (n = 3). (E) HEK293 cells were transfected with EV or Myc-tagged USP15 and treated with DMSO or CCCP (10 µm) for 3 h."
sparser
"Scale bar, 10 mm. (D) Quantification of the percentage of Parkin-positive cells (in the conditions transfected with Parkin and EV) or Parkin-and Myc-positive cells (in the conditions transfected with Parkin and USP15-Myc) in which Parkin colocalized with mitochondria (n ¼ 3). (E) HEK293 cells were transfected with EV or Myctagged USP15 and treated with DMSO or CCCP (10 mM) for 3 h."
reach
"Our present study revealed that in the MCA induced fibrosarcoma model, USP15 deficiency caused hyper-activation of IFN-gamma + T cells, which was associated with formation of a more immunosuppressive tumor microenvironment characterized by upregulated expression of PD-L1 and CXCL12 and enhanced recruitment of Treg cells and MDSCs."
reach
"However, the USP15 deficiency promoted the TCR+CD 28 stimulated production of cytokines, such as interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), in naive CD4 + T cells, as assessed by quantitative real-time RT-PCR (qRT-PCR) (XREF_FIG), intracellular cytokine staining (XREF_FIG) and ELISA (XREF_FIG)."
reach
"Collectively, these data suggest that the CHMP5 and USP15 complex suppresses RANK mediated NF-kappaB activation via IkappaBalpha stabilization in osteoclasts, in which mechanism it prevents proteasomal degradation of IkappaBalpha leading to the retention of NF-kappaB in an inactive cytosolic complex."
sparser
"To examine whether PRP31 interacts directly with USP15, glutathione beads immobilized with a GST-tagged DUSP-UBL domain of USP15 was incubated with PRP31, which was synthesized with the in vitro transcription/translation (IVT/T) in the absence or presence of the SART3 HAT domains."
reach
"To examine whether PRP31 interacts directly with USP15, glutathione beads immobilized with a GST tagged DUSP-UBL domain of USP15 was incubated with PRP31, which was synthesized with the in vitro transcription and translation (IVT/T) in the absence or presence of the SART3 HAT domains."
reach
"Collectively, these data suggest that the CHMP5 and USP15 complex suppresses RANK mediated NF-kappaB activation via IkappaBalpha stabilization in osteoclasts, in which mechanism it prevents proteasomal degradation of IkappaBalpha leading to the retention of NF-kappaB in an inactive cytosolic complex."
USP15 affects signal transduction
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USP15 inhibits signal transduction.
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USP15 activates signal transduction.
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USP15 affects autophagy of mitochondrion
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sparser
"It appeared that GLTSCR2 supported and inhibited the ability of USP15, respectively, to remove K63-linked and K48-linked ubiquitination of RIG-I. These results taken together indicated that GLTSCR2 interacted with RIG-I and USP15 in a complex to support the activity of USP15 to remove K63-linked polyubiquitin chains from RIG-I, leading to inactivation of RIG-I and blockage of IFN-β induction."
USP15 affects Multiple Myeloma
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USP15 activates Multiple Myeloma.
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USP15 inhibits Multiple Myeloma.
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Valproic acid affects USP15
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Valproic acid increases the amount of USP15. 7 / 7
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USP15 affects immune response
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USP15 activates immune response.
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USP15 inhibits immune response.
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"The authors demonstrated that USP15 knockdown significantly inhibited the proliferation, migration, and invasion of hypertrophic scar-derived fibroblasts in vitro and down-regulated the expression of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3; in addition, USP15 overexpression showed the opposite trends (p < 0.05)."
USP15 affects Neoplasm Invasiveness
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USP15 affects Carcinogenesis
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USP15 activates Carcinogenesis.
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USP15 inhibits Carcinogenesis.
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eidos
"USP15 , a deubiquitinase specifically counteracts the parkin-mediated ubiquitination of mitochondria and thus prevents mitophagy , while USP15 knockdown stimulates mitochondrial ubiquitination and age-dependent mitophagy defects in Parkin-deficient muscles and dopaminergic neurons [ 91,106 ] ."
USP15 affects activity
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sparser
"As TRIM25 protein stability is regulated by the balance between degradative K48-linked ubiquitination and USP15-mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG-tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6-TRIM25-USP15 complex."
sparser
"As TRIM25 protein stability is regulated by the balance between degradative K48-linked ubiquitination and USP15-mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG-tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6-TRIM25-USP15 complex."
USP15 affects proteolysis
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USP15 inhibits proteolysis. 5 / 5
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"To investigate Nef role in protein degradation, we seek to identify cellular proteins involved in the UPS mediated protein degradation through association with Nef and found ubiquitin specific protease 15 (USP15) which stabilizes proteins by deubiquitylation and by preventing autoubiquitylation of substrates."
reach
"We found that Nef binds to ubiquitin protein ligase E3A (UBE3A and E6AP) which induces protein degradation by attaching Ub to substrates, i.e. Nef associated with two functionally antagonistic proteins in the UPS mediated protein degradation processes, suggesting that UBE3A could be a major cellular component in regulating USP15 mediated viral protein degradation by interacting with Nef and USP15 simultaneously or independently."
USP15 affects Parkinson Disease
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"The initial screening identified a number of protein candidates in the SUM159‐IL1R2/‐sIL1R2 and MB231‐IL1R2/‐sIL1R2 cells (Table S5, Supporting Information), among them, we did not find the previous reported ubiquitin Ligases or deubiquitinase of BMI1 such as βTrCP,19 RING1B,20 or USP22,21 but we found that IL1R2 could bind to USP15 (Figure
4
A)."
sparser
"The initial screening identified a number of protein candidates in the SUM159‐IL1R2/‐sIL1R2 and MB231‐IL1R2/‐sIL1R2 cells (Table S5, Supporting Information), among them, we did not find the previous reported ubiquitin Ligases or deubiquitinase of BMI1 such as βTrCP, xref RING1B, xref or USP22, xref but we found that IL1R2 could bind to USP15 ( Figure xref A)."
reach
"The initial screening identified a number of protein candidates in the SUM159‐IL1R2/‐sIL1R2 and MB231‐IL1R2/‐sIL1R2 cells (Table S5, Supporting Information), among them, we did not find the previous reported ubiquitin Ligases or deubiquitinase of BMI1 such as βTrCP,19 RING1B,20 or USP22,21 but we found that IL1R2 could bind to USP15 (Figure
4
A)."
sparser
"The initial screening identified a number of protein candidates in the SUM159‐IL1R2/‐sIL1R2 and MB231‐IL1R2/‐sIL1R2 cells (Table S5, Supporting Information), among them, we did not find the previous reported ubiquitin Ligases or deubiquitinase of BMI1 such as βTrCP, xref RING1B, xref or USP22, xref but we found that IL1R2 could bind to USP15 ( Figure xref A)."
sparser
"As TRIM25 protein stability is regulated by the balance between degradative K48-linked ubiquitination and USP15-mediated deubiquitination, the authors performed coimmunoprecipitation experiments in HEK 293T and cervical-carcinoma-derived C33a cells ectopically expressing FLAG-tagged E6 of HPV16, showing that E6 binds exogenous TRIM25 and USP15, giving rise to a ternary E6-TRIM25-USP15 complex."
USP15 affects protein
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USP15 affects pathway
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"The NF‐kB signalling pathway plays critical role in regulation of innate and adaptive immunity, inflammation, apoptosis, cancer and tumour development. xref NF‐kB is a transcription factor, consists of five related proteins, p105/p50 (NF‐κB1) and p100/p52 (NF‐κB2), p65 (RelA), RelB and c‐Rel (Rel), which in resting state remain in the cytoplasm as dimers associated with the IκB inhibitor. xref There are eight IκB proteins, IκBα, IκBβ, IκBε, IκBζ, BCL‐3, IκBns and the precursor proteins NF‐κB2 and NF‐κB1, which are characterized by the presence of six to seven ankyrin repeat motifs (ANK) which have binding ability to NF‐κB dimers. xref , xref Therefore, in unstimulated cells, NF‐κB dimers bind to IκB inhibitor proteins in the cytoplasm because all NF‐κB proteins are characterized by the presence of a highly conserved Rel homology domain (RHD) in their N‐terminus, which contains a nuclear localization signal (NLS) and is responsible interaction with IκBs. xref Upon stimulation, IκB is phosphorylated in serine residues by the IκB kinase (IKK) complex, which consists of two catalytic subunits, IKKα (IKK1 or CHUK) and IKKβ (IKK2) and an NF‐κB essential modifier (NEMO, also known as IKKγ, IKKAP1 or Fip‐3). xref , xref Phosphorylated IκB creates a destruction motif recognized by the ubiquitin ligase complex and degraded by 26S proteasome, then NF‐κB complexes translocate to the nucleus and regulates the expression of its target genes. xref , xref Ubiquitination plays a crucial role in control of NF‐κB pathway as a major regulator of the immune response. xref USP15 inhibits the NF‐κB pathway by removing K48‐Ub from IκBα and consequently prevent degradation it."
USP15 affects Tumor Microenvironment
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USP15 affects RORgammat
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USP15 affects K48-
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"The U4/U6 recycling factor SART3 has histone chaperone activity and associates with USP15 to regulate H2B deubiquitination."
"?Ubp-M may deubiquitinate several critical proteins that are involved in the condensation of mitotic chromosomes, mainly on ubiquitinated proteins of the chromatin such as histones H2A and H2B?"
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"Mechanistically, XOR physically interacts with USP15, thereby promoting deubiquitination of Kelch Like ECH Associated Protein 1 (KEAP1) to stabilize its expression, which leads to degradation of Nrf2 via ubiquitination and subsequently reactive oxygen species (ROS) accumulation in liver CSCs."
sparser
"Mechanistically, XOR physically interacts with USP15, thereby promoting deubiquitination of Kelch Like ECH Associated Protein 1 (KEAP1) to stabilize its expression, which leads to degradation of Nrf2 via ubiquitination and subsequently reactive oxygen species (ROS) accumulation in liver CSCs."
USP4 affects BRAP
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USP15 affects p53-R175H
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USP15 affects interaction RIG-I IPS-1 DUB activity-independent manner
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USP15 affects degradation
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USP15 affects cell growth
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USP15 inhibits cell growth.
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USP15 activates cell growth.
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USP15 activates cell growth. 1 / 1
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"Mechanistically, XOR physically interacts with USP15, thereby promoting deubiquitination of Kelch Like ECH Associated Protein 1 (KEAP1) to stabilize its expression, which leads to degradation of Nrf2 via ubiquitination and subsequently reactive oxygen species (ROS) accumulation in liver CSCs."
sparser
"Mechanistically, XOR physically interacts with USP15, thereby promoting deubiquitination of Kelch Like ECH Associated Protein 1 (KEAP1) to stabilize its expression, which leads to degradation of Nrf2 via ubiquitination and subsequently reactive oxygen species (ROS) accumulation in liver CSCs."
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"At one point, endosomes leave the cloud, which involves the deubiquitination of SQSTM1 and p62 by the deubiquitinating enzyme USP15, and start their fast bidirectional microtubule based journey in the periphery along microtubules and finally the cortical actin cytoskeleton before reaching the cell surface."
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"At one point, endosomes leave the cloud, which involves the deubiquitination of SQSTM1 and p62 by the deubiquitinating enzyme USP15, and start their fast bidirectional microtubule based journey in the periphery along microtubules and finally the cortical actin cytoskeleton before reaching the cell surface."
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"We will discuss the DUBs that influence the pathways of interferons (IFN), tumor necrosis factors (TNF), TNF-related apoptosis-inducing ligand (TRAIL), interleukins (IL) and chemokines.In a study using HEK293 T cells and Sendai virus (SeV), knockdown of the gene transcribing USP15 resulted in upregulation of type I IFN, while overexpression of USP15 decreased type I interferon as USP15 showed dose-dependent inhibition of IFN-β [16]."
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"We will discuss them one by one.In a study using HEK293 T cells and Sendai virus (SeV), knockdown of the gene transcribing USP15 resulted in upregulation of type I IFN, while overexpression of USP15 decreased type I interferon as USP15 showed dose-dependent inhibition of IFN-β [16] ."
USP15 affects Protein Stability
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USP15 affects ISRE
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USP15 affects E3_Ub_ligase
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E3_Ub_ligase binds USP15 and SMAD7. 2 / 2
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E3_Ub_ligase binds USP15, KEAP1, and CUL3. 1 / 1
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"A distinct cross-talk between NF-kappaB pathway and CSN-signalosome was then confirmed by the fact that Jab1 and COPS5 controls NF-kB activity through CSN associated deubiquitinase USP15, which causes deubiquitination of IkappaBalpha, a negative feedback between degradation of IkappaBalpha and activation of NF-kappaB."
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"However, the USP15 deficiency promoted the TCR+CD 28 stimulated production of cytokines, such as interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), in naive CD4 + T cells, as assessed by quantitative real-time RT-PCR (qRT-PCR) (XREF_FIG), intracellular cytokine staining (XREF_FIG) and ELISA (XREF_FIG)."
E3_Ub_ligase affects USP15
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E3_Ub_ligase binds USP15 and SMAD7. 2 / 2
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E3_Ub_ligase binds USP15, KEAP1, and CUL3. 1 / 1
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"A distinct cross-talk between NF-kappaB pathway and CSN-signalosome was then confirmed by the fact that Jab1 and COPS5 controls NF-kB activity through CSN associated deubiquitinase USP15, which causes deubiquitination of IkappaBalpha, a negative feedback between degradation of IkappaBalpha and activation of NF-kappaB."
BRAP affects USP4
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"Paralleling the pHNef expression (lane 2, XREF_FIG), transfection of pYNef expressing R-tropic nef (YU2 strain) of HIV-1 reduced the amount of USP15 (lane 3, XREF_FIG), establishing that the observed decreases of USP15 were not just strain specific but were common to different strains of HIV-1 Nef."
SiUSP15-1 affects USP15
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SiUSP15#2 affects USP15
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SiUSP15#1 affects USP15
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Receptor-activated SMAD affects USP15
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Phenylmercury acetate affects USP15
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Foci affects USP15
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Cobalt dichloride affects USP15
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Bafilomycin A1 affects USP15
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Associated deubiquitinating enzyme Ubp12p affects USP15
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Acrylamide affects USP15
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Acrylamide increases the amount of USP15.
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Acrylamide decreases the amount of USP15.
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USP15 affects tumor immunity
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USP15 affects removal K1299-linked monoubiquitin
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USP15 affects receptor-activated SMAD
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USP15 affects mitoxantrone
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USP15 affects mitochondrial ubiquitination
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USP15 affects interaction
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eidos
"Although we cannot rule out the possibility that USP15 exerts its effects in a third uncharacterized manner , the data in this study demonstrate that USP15 sequesters the interaction between RIG-I and IPS-1 , shedding light on the mechanisms underlying the catalytic-activity-independent antagonism of IFN by USP15 ."
USP15 affects foci
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USP15 affects expression
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USP15 affects cell death
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USP15 activates cell death. 2 / 2
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"In this report, we found that PdPT is an inhibitor of multiple DUBs including USP7, USP10, USP14, USP15, USP25 and UCHL5, which contributes to the accumulation of ubiquitinated proteins and subsequent cell death in NSCLC cell lines.Regulated cell death requires activation of various regulators and effectors (23)."
USP15 affects Ubiquitination
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USP15 affects Th17 differentiation
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USP15 affects TGFbeta receptor
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USP15 affects TGF-beta pathway
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USP15 affects TET2 binding DNA
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USP15 affects SEV-induced phosphorylation NF-kappaB subunit p65 IRF3
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USP15 affects SEV-induced phosphorylation NF-kappa B subunit p65 IRF3
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USP15 affects SEV-induced activation promoter
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"To investigate Nef role in protein degradation, we seek to identify cellular proteins involved in the UPS mediated protein degradation through association with Nef and found ubiquitin specific protease 15 (USP15) which stabilizes proteins by deubiquitylation and by preventing autoubiquitylation of substrates."
USP15 affects OMM proteins
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USP15 affects NP
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"Consistently, USP15 shRNA impaired the protein levels of MMP9, N-cadherin, and Vimentin, but recovered E-cadherin expression in GINS1-overexpressing A172 cells, while the USP15 plasmid restored the protein levels of MMP9, N-cadherin, and Vimentin, but attenuated E-cadherin expression in GINS1-silenced U251 cells (Figure 6Q)."
USP15 affects LUBAC-dependent TRIM25
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USP15 affects L-glutamine
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USP15 activates L-glutamine. 2 / 2
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USP15 affects K63-polyUb
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USP15 affects Imatinib resistance cells
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"Downregulation of USP15 contributes to Imatinib resistance of CML cells Because previously studies have reported that dysregulation of USP15 could result in paclitaxel resistance in HeLa cells [ 9 ] , we wanted to investigate whether USP15 downregulation is associated with CML Imatinib resistance ."
USP15 affects ISRE-Luc
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USP15 affects EIF4A1 protein stability
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eidos
"Moreover , we have observed EIF4A1 protein expression was significantly upregulated ( Figure 5D , 2nd panel ) while the RNA expression of EIF4A1 remain unchanged ( Supplementary Figure S6B ) which demonstrated that USP15 could interact with and deubiquitinate EIF4A1 , thus promoting EIF4A1 protein stability ."
USP15 affects Cicatrix, Hypertrophic
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USP15 affects Cell Survival
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USP15 activates Cell Survival. 1 / 2
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USP15 affects C-terminal domain of RIG-I
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USP15 affects BMP receptors
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USP15 affects Adenocarcinoma of Lung
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SMAD7 affects E3_Ub_ligase
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"However, we were unable to observe an effect of USP15 depletion on luciferase transcription driven from a previously described CRAF-promoter, although we can not fully exclude that USP15 may regulate CRAF transcription via an upstream or downstream element not contained in this 1.2-kb promoter construct."
PRP-Exos affects USP15
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NP affects USP15
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Interferon affects USP15
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E3_Ub_ligase affects SMAD7, and USP15
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C-terminal domain of RIG-I affects USP15
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BMP receptors affects USP15
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PLVX-Puro-USP15 affects USP15
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P53-R175H affects USP15
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Methyl methanesulfonate affects USP15
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Methotrexate affects USP15
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Manganese(II) chloride affects USP15
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Hsa-miR-7853-5p affects USP15
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Hsa-miR-607 affects USP15
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Hsa-miR-520g-3p affects USP15
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Hsa-miR-520c-3p affects USP15
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Hsa-miR-520b affects USP15
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Hsa-miR-497-5p affects USP15
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Hsa-miR-373-3p affects USP15
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Hsa-miR-302e affects USP15
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Hsa-miR-222-3p affects USP15
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Curcusone D affects USP15
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Benzo[e]pyrene affects USP15
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Aflatoxin B1 affects USP15
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YP_009227201 affects USP15
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USP15 affects α-SMA
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USP15 affects oncogenic capacity patient-derived glioma-initiating cells owing TGFbeta signalling
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USP15 affects lysosome-mediated R175H mutp53
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USP15 affects homologous recombination
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USP15 activates homologous recombination. 1 / 1
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USP15 affects hepatocellular carcinoma
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USP15 inhibits hepatocellular carcinoma. 1 / 1
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USP15 affects global 5hmC
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USP15 affects functions several proteins involved signaling pathways
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USP15 affects cytokine production
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USP15 inhibits cytokine production. 1 / 1
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USP15 affects cell viability ovarian cancer cells expressing p53-R175H mutant protein
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USP15 affects autophagy cargo receptor
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USP15 affects apoptosis degenerative nucleus pulposus cells
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USP15 affects activation NF-kappaB p = 1.92E-04 IRF3 p = 1.04E-03 reporter assays
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USP15 affects aberrant CARD9
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USP15 affects YP_009227201
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USP15 affects USP15 mitophagy depended
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USP15 affects UBL
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USP15 affects TET2 binding substrate DNA Monoubiquitylation TET2
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USP15 affects TET binding TET
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USP15 affects TCR+CD28
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"However, the USP15 deficiency promoted the TCR+CD 28 stimulated production of cytokines, such as interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), in naive CD4 + T cells, as assessed by quantitative real-time RT-PCR (qRT-PCR) (XREF_FIG), intracellular cytokine staining (XREF_FIG) and ELISA (XREF_FIG)."
USP15 affects T cell responses
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USP15 affects RP23-440M18.7
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USP15 affects RIG-I-N
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USP15 affects R-SMADs
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USP15 affects R-SMAD
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USP15 affects R-SMAD monoubiquitination
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USP15 affects Oxidative Stress
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USP15 inhibits Oxidative Stress. 1 / 1
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USP15 affects Nrf2/HO-1
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USP15 affects NUP153
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USP15 affects Lys734 ubiquitination
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USP15 affects Lymphatic Metastasis
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USP15 activates Lymphatic Metastasis. 1 / 1
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"Mechanistic dissection further revealed that MFSD4A-AS1 functioned as ceRNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNAs-mediated inhibition of VEGFA and VEGFC, and further activated TGF-β signaling by sponging miR-30c-2-3p that targeted TGFBR2 and USP15, both of which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC."
USP15 affects Luc
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USP15 affects K63-linked ubiquitination RIG-I-N
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USP15 affects IPS-1-RIG-I binding
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USP15 affects IFNs independent DUB
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USP15 affects IFN1
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USP15 affects Hemagglutinins
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USP15 affects Harhaj
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"In addition, USP15 overexpression reversed the inhibited proliferation and migration ability of glioma cells induced by GINS1 silencing in U251 cells, whereas USP15 knockdown impaired the elevated proliferation and migration ability of glioma cells induced by GINS1 overexpression in A72 cells."
USP15 affects DNA Damage
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USP15 activates DNA Damage. 1 / 1
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USP15 affects Cul3-Keap1-E3 ubiquitin
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E3_Ub_ligase binds USP15, KEAP1, and CUL3. 1 / 1
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USP15 affects Adaptor_protein_III
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USP15 activates Adaptor_protein_III. 1 / 1
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USP15 affects 5hmC mouse liver
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USP15 affects 3-methylcholanthrene
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USP15 inhibits 3-methylcholanthrene. 1 / 1
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USP15 sgRNA A1 CCAAGTTACTTAGGCCACAG sgRNA B2 affects USP15
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UBL affects USP15
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TIFAB mutant affects USP15
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TGIF affects USP15
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SMAD affects Hemagglutinins
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SART3 affects UBL
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Radiation, Ionizing affects USP15
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Radiation, Ionizing activates USP15. 1 / 1
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RP23-440M18.7 affects USP15
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RIG-I-N affects USP15
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R-SMADs affects USP15
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"It appeared that GLTSCR2 supported and inhibited the ability of USP15, respectively, to remove K63-linked and K48-linked ubiquitination of RIG-I. These results taken together indicated that GLTSCR2 interacted with RIG-I and USP15 in a complex to support the activity of USP15 to remove K63-linked polyubiquitin chains from RIG-I, leading to inactivation of RIG-I and blockage of IFN-β induction."
eidos
"USP15 is a direct target of miR-202-5p Because we found that USP15 downregulation led to decreased apoptosis in CML cells by lowering the level of Caspase-6 protein , we sought to know whether the expression of USP15 is suppressed in CML cells by a microRNA that targets 3 ' - untranslated region ( 3 ' - UTR ) of USP15 mRNA ."
KEAP1 affects E3_Ub_ligase
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E3_Ub_ligase binds USP15, KEAP1, and CUL3. 1 / 1
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Hemagglutinins affects USP15
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E3_Ub_ligase affects KEAP1
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E3_Ub_ligase binds USP15, KEAP1, and CUL3. 1 / 1
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DUSP affects UBL
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sparser
"It appeared that GLTSCR2 supported and inhibited the ability of USP15, respectively, to remove K63-linked and K48-linked ubiquitination of RIG-I. These results taken together indicated that GLTSCR2 interacted with RIG-I and USP15 in a complex to support the activity of USP15 to remove K63-linked polyubiquitin chains from RIG-I, leading to inactivation of RIG-I and blockage of IFN-β induction."
E3_Ub_ligase binds USP15, KEAP1, and CUL3. 1 / 1
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4-hydroxyphenyl retinamide affects USP15
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17alpha-ethynylestradiol affects USP15
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