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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"However, Tip110 was found to interact with and promote nuclear translocation of USP4 and USP15 but not USP11, and this is due to β-hairpin of the linker region of the DUSP and UBL domains of both USP4 and USP15 proteins that were associated with the HAT domain of Tip110 (12, 23, 25, 38) In addition, the binding of USP15 to Tip110 is 20-fold stronger than USP4 (55)."
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"These data further confirming the opposing effect of Tip110 and USP15 on IκBα stability.As we previously alluded to, Tip110 expression promoted the nuclear translocation of USP15 where both are associated (25) and the above observations prompted us to examine whether Tip110 also targeted nuclear IκBα to regulate NF-κB activity."
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"The complex structure of the NLS on Tip110 and importin 2α is involved a bipartite binding, and removal of Tip110 NLS prevents the entry of USP4 or USP15 in the nucleus and abrogates their subsequent deubiquitinase activity (12, 55), which may explain the detection of a higher ubiquitinated form of cytoplasmic expressed Tip110ΔNLS mutant (
Figures 2D
,
4C, E
)."
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"However, Tip110 was found to interact with and promote nuclear translocation of USP4 and USP15 but not USP11, and this is due to β-hairpin of the linker region of the DUSP and UBL domains of both USP4 and USP15 proteins that were associated with the HAT domain of Tip110 (12, 23, 25, 38) In addition, the binding of USP15 to Tip110 is 20-fold stronger than USP4 (55)."
USP15 affects cell population proliferation
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USP15 activates cell population proliferation.
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USP15 activates cell population proliferation. 10 / 61
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USP15 bound to PARP1 activates cell population proliferation. 2 / 2
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USP15 inhibits cell population proliferation.
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USP15 inhibits cell population proliferation. 8 / 8
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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."
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"Whereas, knock-down of USP15 dramatically inhibited tumor cell proliferation evidenced by CCK8 and colony formation assays, within K1 and 8505 C, which both represent BRAF -mutated thyroid cancer cells [K1 represents PTC cells, 8505 C represents ATC cells] (Fig. 3a, b, Supplementary Fig. 2d−f)."
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."
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"Mechanistically, USP15 can activate the transforming growth factor β (TGF-β) signaling pathway and promote the progression of advanced malignant glioma by combining the SMAD-specific E3 ubiquitin protein ligase 2 complex and deubiquitinating and thus stabilizing the TGF b type I receptor[13]."
eidos
"USP15 Enhances TGF-beta Signaling by Deubiquitinating the Type I TGFbeta Receptor ALK5 The TGF-beta signaling pathway is involved in diverse cellular processes in both the developing embryo and the adult organism ; these processes include cell growth and differentiation , immune response , apoptosis , cellular homeostasis , wound healing , and many other functions ."
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"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)."
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"Furthermore, either silencing TGFBR2 or USP15 or blocking activity of TGF-β signaling using LY2109761, a novel selective TGF-β receptor type I/II dual inhibitor (Melisi et al. 2008), differentially abrogated the stimulatory effect of MFSD4A-AS1 on invasive and migration abilities of PTC cells (Supplementary Fig. 6A and B)."
sparser
"However, Tip110 was found to interact with and promote nuclear translocation of USP4 and USP15 but not USP11, and this is due to β-hairpin of the linker region of the DUSP and UBL domains of both USP4 and USP15 proteins that were associated with the HAT domain of Tip110 ( xref , xref , xref , xref ) In addition, the binding of USP15 to Tip110 is 20-fold stronger than USP4 ( xref )."
sparser
"However, Tip110 was found to interact with and promote nuclear translocation of USP4 and USP15 but not USP11, and this is due to β-hairpin of the linker region of the DUSP and UBL domains of both USP4 and USP15 proteins that were associated with the HAT domain of Tip110 ( xref , xref , xref , xref ) In addition, the binding of USP15 to Tip110 is 20-fold stronger than USP4 ( xref )."
USP15 affects Neoplasm Invasiveness
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USP15 activates Neoplasm Invasiveness.
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USP15 activates Neoplasm Invasiveness. 10 / 45
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USP15 activates Neoplasm Invasiveness. 3 / 3
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USP15 inhibits Neoplasm Invasiveness.
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"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]."
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"Conversely, downregulation of HOXA9 by RelB and upregulation of HOXA9 by RelA (Figure 1D) suggest that non-canonical and canonical signaling differentially regulate Hoxa9 expression.TIFAB has recently been shown to increase leukemia progenitor cell functions through regulation of ubiquitin-specific peptidase 15 ubiquitin hydrolase activity to repress p53 (Niederkorn et al., 2020b)."
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"In melanoma and colorectal cell lines, deletion of USP15 induces MDM2 auto-ubiquitination and degradation and USP15 negatively regulates the T-cell transcription factor NFATc2 by decreasing MDM2 auto-ubiquitination and degradation, thereby inhibiting T-cell proliferation and activation (Fig. 2C).35However, MDM2 inhibits T cell apoptosis and promotes T cell proliferation and activation."
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"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
"The antagonistic actions between ubiquitin ligases and DUBs are responsible for protein homeostasis as exemplified that USP13-FBXL14 regulated reversible ubiquitination of c-Myc in glioblastoma stem cells [ xref ], and USP15-SMURF2 cooperatively modulated TGF-β receptor in glioblastoma [ xref ]."
"<span class="match term0">USP15</span> specifically removed lysine 63-linked polyubiquitin chains from <span class="match term1">RIG-I</span> among the essential components in <span class="match term1">RIG-I</span>-like receptor-dependent pathway"
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"Along a similar research line, our study showed that miR-26a serves as a potent positive regulator of IFN responses, highlighting the potential that miR-26a or its mimics can be further explored as a broad antiviral agent.On the other hand, in our study, we found that USP15 suppressed the type I interferon signaling by removing K63-linked of RIG-I ubiquitination, which is consistent with one previous research (24) but contrary with the results described in Pauli’s paper (37)."
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"TGF-β activity in GBM is modulated by several deubiquitinating enzymes (DUBs); first, it was described that TGF-β activity could be enhanced due to the amplification of a deubiquitinating enzyme, USP15, which binds to the SMAD7–SMURF2 complex and stabilizes type I TGF-β receptors, resulting in enhanced TGF-β signaling."
SMAD7 binds E3_Ub_ligase and USP15. 2 / 2
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USP15 binds E6.
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"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
"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."
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"TGF-β activity in GBM is modulated by several deubiquitinating enzymes (DUBs); first, it was described that TGF-β activity could be enhanced due to the amplification of a deubiquitinating enzyme, USP15, which binds to the SMAD7–SMURF2 complex and stabilizes type I TGF-β receptors, resulting in enhanced TGF-β signaling."
SMAD7 binds E3_Ub_ligase and USP15. 2 / 2
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"Immunoprecipitation of USP15 and its mutant proteins with anti-Myc antibody, followed by WB with anti-GFP antibody for the detection of Nef.GFP and GFP, showed that Nef.GFP, not GFP, was detected only in the cells transfected with wild type- or USPDeltaN-, but not with USPDeltaC expressing plasmids (XREF_FIG bottom panel), indicating that Nef binds USP15 through the encoded protein motif (s) from amino acid 385 to the end of the USP15 gene."
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"Similarly, the amount of Nef was least in the cells transfected with pUSP15, as well as less in the cells transfected with pUSP15DeltaN than in the cells transfected with pUSP15DeltaC (XREF_FIG), establishing that interaction of USP15 and Nef is essential for the reciprocal protein decay."
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"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)."
sparser
"The antagonistic actions between ubiquitin ligases and DUBs are responsible for protein homeostasis as exemplified that USP13-FBXL14 regulated reversible ubiquitination of c-Myc in glioblastoma stem cells [ xref ], and USP15-SMURF2 cooperatively modulated TGF-β receptor in glioblastoma [ xref ]."
E6 binds USP15.
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"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
"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."
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"Immunoprecipitation of USP15 and its mutant proteins with anti-Myc antibody, followed by WB with anti-GFP antibody for the detection of Nef.GFP and GFP, showed that Nef.GFP, not GFP, was detected only in the cells transfected with wild type- or USPDeltaN-, but not with USPDeltaC expressing plasmids (XREF_FIG bottom panel), indicating that Nef binds USP15 through the encoded protein motif (s) from amino acid 385 to the end of the USP15 gene."
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"Similarly, the amount of Nef was least in the cells transfected with pUSP15, as well as less in the cells transfected with pUSP15DeltaN than in the cells transfected with pUSP15DeltaC (XREF_FIG), establishing that interaction of USP15 and Nef is essential for the reciprocal protein decay."
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"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."
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"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)."
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"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."
USP15 affects apoptotic process
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USP15 inhibits apoptotic process.
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USP15 activates apoptotic process.
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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."
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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."
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"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
"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."
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"Taken together, reactivated Tbx3 by BRAF plays the same role as in embryonic development, which is to confine the differentiation state.Strikingly, Usp15 removal dramatically abrogated Tbx3 protein expression from E14.5 thyroid without affecting the mRNA level (Fig. 6c and Supplementary Fig. 5b), thus caused similar developmental defects in terms of disorganized folliculogenesis and elevated differentiation factors, such as Tpo, Tg, and Nis (Fig. 7d)."
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."
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."
USP15 affects cell differentiation
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USP15 activates cell differentiation.
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USP15 inhibits cell differentiation.
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"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."
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."
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"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."
USP15 affects Interferon
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USP15 inhibits Interferon.
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USP15 inhibits Interferon. 9 / 10
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"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."
USP15 activates Interferon.
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USP15 activates Interferon. 6 / 6
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"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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USP15 affects Stomach Neoplasms
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"Thus, USP15 promotes tumor cell proliferation and tumor growth through maintaining TBX3 level and related downstream events.To understand how the proteostasis regulation fits in the in vivo highly spontaneous BRAF -induced tumorigenesis where Tbx3 is re-activated and critically required for tumor initiation and progression , we first collected tumor tissues from mPTC model generated by crossing thyroid peroxidase TPO-Cre with LSL-Braf (Supplementary Fig. 2h) ."
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"Employing colon orthotopic and metastatic tumor models, we performed loss- and gain-of-function assays for USP15, and revealed that over-expression of USP15 promotes tumor progression by increasing the abundance of myeloid-derived suppressor cells (MDSCs) and decreasing the presence of CD8+T cells in the TME."
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"As such, Usp15 appears to function as a double-edged sword in pancreatic cancer, where the loss of Usp15 enhances tumor progression in the initial stages of tumorigenesis but sensitizes to certain treatment regimens in the later stages.Given the wide range of USP15 substrates and USP15-regulated pathways with well-known functions in cancer, we set out to elucidate USP15’s exact role in PDAC suppression."
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"Additionally, the silencing of FOXC1 ameliorated the therapeutic effect of oe-USP15/Exo on LPS-injured chondrocytes.In summary, our research findings elucidates that USP15-modified ADMSCs-derived Exos induces macrophage polarization towards the M2 phenotype by promoting FOXC1 deubiquitination, thereby effectively reducing the degree of chondrocyte damage in OA."
Mitoxantrone affects USP15
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Mitoxantrone inhibits USP15.
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Mitoxantrone binds USP15.
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Mitoxantrone binds USP15. 4 / 4
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"The crystal structure of the USP15-mitoxantrone complex revealed predominantly hydrophobic interactions between mitoxantrone and USP15 residues Tyr855, Gly856, Gly860, and His862, which are located near the catalytic Cys269 [245].2-DGIn cancer, 2-deoxy-d-glucose (2-DG) interferes with D-glucose metabolism to decrease its proliferation [246]."
USP15 affects signal transduction
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USP15 activates signal transduction.
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USP15 inhibits signal transduction.
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"One of the key substrates regulated by the TIFAB-USP15 axis includes p53. xref Deletion of TIFAB sensitizes hematopoietic cells to a variety of cellular stressors, which are dependent on p53 activation. xref Gene set enrichment analysis (GSEA) revealed that a p53-related gene signature was positively enriched inTifab -/- ;miR-146a -/- LSK cells treated with LPS compared to vehicle-treatedTifab -/- ;miR-146a -/- cells, while there was no significant enrichment of a p53-related signature in WT cells treated with LPS ( xref )."
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"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
"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."
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
"One of the key substrates regulated by the TIFAB-USP15 axis includes p53. xref Deletion of TIFAB sensitizes hematopoietic cells to a variety of cellular stressors, which are dependent on p53 activation. xref Gene set enrichment analysis (GSEA) revealed that a p53-related gene signature was positively enriched inTifab -/- ;miR-146a -/- LSK cells treated with LPS compared to vehicle-treatedTifab -/- ;miR-146a -/- cells, while there was no significant enrichment of a p53-related signature in WT cells treated with LPS ( xref )."
"Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15."
sparser
"Immunofluorescence microscopy confirmed that (i) most of the cells in the pool uniformly expressed the transgene after 24 h of induction and (ii) that FF-USP15 WT and CS mutant localise to both cytosolic and nucleoplasmic compartments as previously reported for endogenous USP15 ( xref ) ( xref )."
sparser
"In agreement with our Western blot results ( xref ), we noticed an overall decrease in signal intensity for FF-USP15 CS in cells treated with A/C. We reasoned that this may reflect bystander degradation because of complex formation with CTLA4 and subsequent rapid shuttling of ubiquitylated CTLA4-USP15 CS heterodimers to the lysosome."
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"In our study, knockdown of USP15 significantly reduced the nuclear expression of β-catenin and downregulation of Wnt/β-catenin downstream genes in GC cells, while USP15 overexpression yielded opposite results, and there was no change in the USP15 C269S group (USP15 mutant), indicating that USP15 acted as a Wnt/β-catenin pathway activator."
sparser
"Immunofluorescence microscopy confirmed that (i) most of the cells in the pool uniformly expressed the transgene after 24 h of induction and (ii) that FF-USP15 WT and CS mutant localise to both cytosolic and nucleoplasmic compartments as previously reported for endogenous USP15 ( xref ) ( xref )."
sparser
"In agreement with our Western blot results ( xref ), we noticed an overall decrease in signal intensity for FF-USP15 CS in cells treated with A/C. We reasoned that this may reflect bystander degradation because of complex formation with CTLA4 and subsequent rapid shuttling of ubiquitylated CTLA4-USP15 CS heterodimers to the lysosome."
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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USP15 binds Proteasome.
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"Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15."
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."
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."
CGAS affects USP15
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"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 )."
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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."
"SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors. Dissociation of the RNF26/SQSTM1 complex, promoted by the DUB USP15 (yellow), releases target vesicles for (4) fast transport into the cell periphery."
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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."
sparser
"For example, USP15 can deubiquitinate and stabilize the murine double minute 2 (MDM2) protein to hinder cancer cell survival, xref and it can deubiquitinate and suppress the activation of the ten-eleven translocation 2 (TET2) protein, thereby diminishing tumor immunogenicity. xref Additionally, USP15 can interact with sequestosome−1 (SQSTM1) to abolish the activation of ring finger protein 26 (RNF26), facilitating the release of diverse vesicles for fast transport and utilization of intracellular substances. xref A recent study has indicated an elevated expression of USP15 in HCC tumor tissues, revealing a close association with metastasis and poor prognosis. xref Thus, gaining a thorough understanding of this crucial modification implicated in the regulation of HCC progression could offer novel perspectives for cancer therapeutics."
"SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors. Dissociation of the RNF26/SQSTM1 complex, promoted by the DUB USP15 (yellow), releases target vesicles for (4) fast transport into the cell periphery."
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"Results:.
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 TbetaRI, Smad2, Smad3, alpha-SMA, COL1, and COL3; in addition, USP15 overexpression showed the opposite trends (p < 0.05)."
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"Quantitative real-time polymerase chain reaction and Western blot analysis indicated that USP15 knockdown significantly reduced the mRNA and protein expression levels of TβRI, Smad2, and Smad3 and the fibrosis markers α-SMA, COL1, and COL3; USP15 overexpression showed the opposite trends."
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"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)."
sparser
"NKD1 promotes the ubiquitination degradation of APC by prohibiting the expression of USP15 and blocking binding of the deubiquitinating enzyme USP15 to APC and leads to the entry of β‐catenin into the nucleus to promote colon cancer cell proliferation, migration, and invasion, while let‐7b‐5p inhibits this process by targeting NKD1 (Figure xref )."
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"Furthermore, the knockdown of USP15 could also reduce the migration and invasion capacity of PTC cells as evaluated by transwell invasion assays (Figures 5C and 5D) (PTC cell VS Ctrl, P<0.001) and wound healing (Figures 5E and 5F) (PTC cell VS Ctrl, P<0.001), whereas this phenomenon was reversed in USP15 overexpressed B-CPAP cells (Figures 5G and 5H) (PTC cell VS Vector P<0.001)."
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"In the current study, our results found that MFSD4A-AS1 functioned as ceRNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of VEGFA and VEGFC on the one hand; on the other hand, MFSD4A-AS1 further activated TGF-β signaling by sponging miR-30c-2-3p to relieve the repressive effect of miR-30c-2-3p on TGFBR2 and USP15, which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC."
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"Mechanistic dissection further revealed that MFSD4A-AS1 functioned as competing endogenous RNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of vascular endothelial growth factors A and C, and further activated transforming growth factor (TGF)-beta 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 autophagy of mitochondrion
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USP15 inhibits autophagy of mitochondrion.
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8
USP15 activates autophagy of mitochondrion.
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2
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"Co-immunoprecipitation and ubiquitination assays showed that USP15 knockdown significantly increased the TβRI ubiquitination levels in hypertrophic scar–derived fibroblasts, whereas USP15 overexpression significantly reduced the TβRI ubiquitination levels in hypertrophic scar–derived fibroblasts."
reach
"Quantitative real-time polymerase chain reaction and Western blot analysis indicated that USP15 knockdown significantly reduced the mRNA and protein expression levels of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3 (0.51 ± 0.01-fold versus 1.68 ± 0.06-fold, 0.58 ± 0.01-fold versus 1.30 ± 0.03-fold, 0.25 ± 0.03-fold versus 1.23 ± 0.04-fold, 0.44 ± 0.06-fold versus 0.88 ± 0.06-fold, 0.83 ± 0.09-fold versus 1.61 ± 0.07-fold, and 0.42 ± 0.03-fold versus 1.03 ± 0.03-fold; p < 0.05)."
reach
"Quantitative real-time polymerase chain reaction and Western blot analysis indicated that USP15 knockdown significantly reduced the mRNA and protein expression levels of TβRI, Smad2, and Smad3 and the fibrosis markers α-SMA, COL1, and COL3; USP15 overexpression showed the opposite trends."
USP15 affects Cicatrix, Hypertrophic
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10
USP15 activates Cicatrix, Hypertrophic.
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USP15 activates Cicatrix, Hypertrophic. 8 / 8
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8
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"Cell Counting Kit-8 assays showed that USP15 knockdown significantly inhibited the proliferation of hypertrophic scar–derived fibroblasts (62.06 ± 10.46 percent; p < 0.05), whereas USP15 overexpression significantly promoted the proliferation of hypertrophic scar–derived fibroblasts (147.97 ± 10.49 percent; p < 0.05."
reach
"(Center, right) The migration of hypertrophic scar fibroblasts in blank, vector, and USP15 groups was detected by scratch assays (*p < 0.05), http://links.lww.com/PRS/E645.] Scratch assays showed that USP15 knockdown significantly inhibited the migration of hypertrophic scar–derived fibroblasts (79.25 ± 0.71 percent; p < 0.05), whereas USP15 overexpression significantly promoted the migration of hypertrophic scar–derived fibroblasts (163.84 ± 0.21 percent; p < 0.05) (see Figure, Supplemental Digital Content 2, http://links.lww.com/PRS/E645)."
reach
"Matrigel invasion assays showed that USP15 knockdown significantly inhibited the invasion of hypertrophic scar–derived fibroblasts (0.37 ± 0.03-fold; p < 0.05), whereas USP15 overexpression significantly promoted the invasion of hypertrophic scar–derived fibroblasts (2.17 ± 0.11-fold; p < 0.05)."
reach
"(Right) The invasion of hypertrophic scar fibroblasts in blank, vector, and USP15 groups was detected by Matrigel invasion assays (*p < 0.05), http://links.lww.com/PRS/E646.] These results suggest that USP15 promotes the proliferation, migration, and invasion of hypertrophic scar–derived fibroblasts."
USP15 inhibits Cicatrix, Hypertrophic.
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2
USP15 inhibits Cicatrix, Hypertrophic. 2 / 2
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2
reach
"Co-immunoprecipitation and ubiquitination assays showed that USP15 knockdown significantly increased the TβRI ubiquitination levels in hypertrophic scar–derived fibroblasts, whereas USP15 overexpression significantly reduced the TβRI ubiquitination levels in hypertrophic scar–derived fibroblasts."
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."
reach
"As expected, our current investigation showed that CHMP5 was capable of binding USP15 to inhibit IκBα ubiquitination, thereby suppressing enhanced apoptosis and ECM degradation induced by IL-1β through NF-κB signaling pathway in OA chondrocytes.Taken together, CHMP5 alleviates OA development by decreasing OA chondrocyte apoptosis and ECM degradation caused by IL-1β via NF-κB signaling pathway (Fig. 8)."
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."
reach
"As expected, our current investigation showed that CHMP5 was capable of binding USP15 to inhibit IκBα ubiquitination, thereby suppressing enhanced apoptosis and ECM degradation induced by IL-1β through NF-κB signaling pathway in OA chondrocytes.Taken together, CHMP5 alleviates OA development by decreasing OA chondrocyte apoptosis and ECM degradation caused by IL-1β via NF-κB signaling pathway (Fig. 8)."
reach
"Results:.
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 TbetaRI, Smad2, Smad3, alpha-SMA, COL1, and COL3; in addition, USP15 overexpression showed the opposite trends (p < 0.05)."
reach
"Quantitative real-time polymerase chain reaction and Western blot analysis indicated that USP15 knockdown significantly reduced the mRNA and protein expression levels of TβRI, Smad2, and Smad3 and the fibrosis markers α-SMA, COL1, and COL3; USP15 overexpression showed the opposite trends."
sparser
"To determine whether USP15 regulates CBX5 ubiquitination and, thus, affects its expression, we first used an anti-CBX5 antibody to precipitate CBX5 in control and hypoxic PASMCs and found USP15 in those immune precipitates ( xref ), indicating that USP15 can bind to CBX5 in PASMCs."
reach
"To determine whether USP15 regulates CBX5 ubiquitination and, thus, affects its expression, we first used an anti-CBX5 antibody to precipitate CBX5 in control and hypoxic PASMCs and found USP15 in those immune precipitates (Figure 5B), indicating that USP15 can bind to CBX5 in PASMCs."
reach
"This study investigated PH-related molecular interactions in PASMCs and found: 1) RUNX1 promotes hypoxia-induced PASMC dysfunction and PH; 2) RUNX1 transcriptionally activates the expression of USP15; 3) USP15 reduces CBX5 ubiquitination and promotes CBX5 expression; and 4) RUNX1 regulates PASMC function through the USP15/CBX5 axis.RUNX1 is a master developmental regulator essential for hematopoietic cell differentiation and normal hematopoiesis [21]."
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."
USP15 affects immune response
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8
USP15 inhibits immune response.
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4
USP15 activates immune response.
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4
reach
"To determine if ectopic USP15 and UbV expression could also alter YY1 transcription and subsequently contribute to changes in YY1 protein expression, we transfected 293T with pNL4-3 and with or without pUSP15-Myc or pFlag-UbV15.1, isolated total RNA, and performed qRT-PCR for the YY1 mRNA level."
reach
"The results showed that neither ectopic USP15 expression nor UbV expression resulted in any apparent changes in YY1 mRNA expression when compared to the control or to each other (
Figure 7
), indicating that changes of YY1 protein expression by ectopic USP15 and UbV expression are unlikely to occur at the transcription level, and rather at the post-translational level.3.6
Ectopic USP15 and UbV expression altered YY1 ubiquitination."
sparser
"Studies by Tong et al. revealed that in breast cancer EMT, PLOD2 is associated with increased cytoplasmic succinate, driving mesenchymal transformations and enhancing cancer cell stemness while reducing 5-hydroxymethylcytosine (5hmC) levels in chromatin upon silencing of PLOD2. xref Additionally, Lan et al. uncovered a critical interaction between PLOD2 and USP15, a deubiquitinating enzyme, that stabilizes and activates the AKT/mTOR signaling pathway, consequently fostering the progression of colorectal cancer. xref This interaction underscores the emerging complexities of PLOD2ʼs role in cancer signaling networks."
USP15 affects Multiple Myeloma
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8
USP15 activates Multiple Myeloma.
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5
USP15 inhibits Multiple Myeloma.
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3
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)."
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)."
USP15 affects DNA-templated transcription
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8
USP15 inhibits DNA-templated transcription.
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5
USP15 inhibits DNA-templated transcription. 5 / 5
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5
reach
"Ectopic USP15 expression deubiquitinates and stabilizes endogenous YY1 and thus suppresses HIV-1 transcription, while USP15-specific UbV inhibitors prevent endogenous USP15 from deubiquitinating YY1, thus promoting YY1 degradation and relieving USP15-induced inhibition of HIV-1 transcription."
reach
"These results collectively demonstrated the inhibitory effects of USP15 on HIV-1 gene expression and virus production and suggest the important roles of USP15 in HIV infection and pathogenesis.3.2
Ectopic USP15 expression repressed HIV-1 transcription, whereas UbV expression increased HIV-1 transcription."
reach
"Using the USP15 UbV inhibitors, we demonstrated that ectopic USP15 expression inhibited HIV-1 transcription, contributing to decreased HIV-1 gene expression and virus production, whereas expression of UbV, USP15 inhibitors, had opposite effects on HIV-1 transcription, gene expression and virus production."
USP15 activates DNA-templated transcription.
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3
USP15 affects Carcinogenesis
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2
6
USP15 activates Carcinogenesis.
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1
4
USP15 inhibits Carcinogenesis.
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1
2
reach
"Moreover, the activation of USP15 by TFAP4 as a transcription factor was validated by the following ChIP and pull‐down assay, which would provide a novel theoretical basis for a deeper understanding of renal carcinogenesis.Collectively, our study demonstrated that USP15 upregulation accelerates ccRCC malignant behavior, which may attributed to increased SHC1 stabilization via deubiquitination."
sparser
"Studies by Tong et al. revealed that in breast cancer EMT, PLOD2 is associated with increased cytoplasmic succinate, driving mesenchymal transformations and enhancing cancer cell stemness while reducing 5-hydroxymethylcytosine (5hmC) levels in chromatin upon silencing of PLOD2. xref Additionally, Lan et al. uncovered a critical interaction between PLOD2 and USP15, a deubiquitinating enzyme, that stabilizes and activates the AKT/mTOR signaling pathway, consequently fostering the progression of colorectal cancer. xref This interaction underscores the emerging complexities of PLOD2ʼs role in cancer signaling networks."
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
"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
"NKD1 promotes the ubiquitination degradation of APC by prohibiting the expression of USP15 and blocking binding of the deubiquitinating enzyme USP15 to APC and leads to the entry of β‐catenin into the nucleus to promote colon cancer cell proliferation, migration, and invasion, while let‐7b‐5p inhibits this process by targeting NKD1 (Figure xref )."
Valproic acid affects USP15
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Valproic acid increases the amount of USP15. 7 / 7
7
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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."
reach
"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."
USP15 affects pathway
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7
USP15 activates pathway.
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4
USP15 inhibits pathway.
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3
sparser
"It has been reported in that USP15 is highly expressed in gastric cancer, promoting malignant progression by activating the Wnt/β-catenin pathway [ xref ], however, other studies have found that USP15 can inhibit the NF-κB pathway by deubiquitinating IκB-α, thereby inhibiting the proliferation and invasion of gastric cancer [ xref ]."
sparser
"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."
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."
reach
"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
"In innate immunity, the cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)pathway, a core DNA sensing mechanism, undergoes multi-level regulation by USP15 deubiquitination: USP15 activates cGAS via deubiquitination and feeds back positively to promote its dimerization and phase separation."
sparser
"In innate immunity, the cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)pathway, a core DNA sensing mechanism, undergoes multi-level regulation by USP15 deubiquitination: USP15 activates cGAS via deubiquitination and feeds back positively to promote its dimerization and phase separation."
reach
"This study investigated PH-related molecular interactions in PASMCs and found: 1) RUNX1 promotes hypoxia-induced PASMC dysfunction and PH; 2) RUNX1 transcriptionally activates the expression of USP15; 3) USP15 reduces CBX5 ubiquitination and promotes CBX5 expression; and 4) RUNX1 regulates PASMC function through the USP15/CBX5 axis.RUNX1 is a master developmental regulator essential for hematopoietic cell differentiation and normal hematopoiesis [21]."
USP15 affects wound healing
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1
5
USP15 affects activity
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6
USP15 affects FKBP*
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6
USP15 affects E3_Ub_ligase
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4
2
USP15 binds E3_Ub_ligase.
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2
2
USP15 deubiquitinates E3_Ub_ligase.
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2
FKBP* affects USP15
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6
USP15 affects proteolysis
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5
USP15 inhibits proteolysis. 5 / 5
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5
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."
reach
"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."
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 inflammatory response
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4
USP15 activates inflammatory response. 5 / 5
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1
4
reach
"Researchers discovered that The expression of the deubiquitinating enzyme USP15 is upregulated in the livers of HFD-fed mice and in liver biopsy tissues from patients with NAFLD or NASH, whereas hepatocyte deletion of USP15 suppresses hepatic steatosis, inflammation, and fibrosis in a mouse model of NASH (133)."
USP15 affects DNA Damage
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5
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
"On further exploration, we found that knockdown of USP15 did not affect the interaction between ACVRL1 and GPX2 (Additional file 1: Figure S3C); similarly, knockdown of GPX2 also did not affect the interaction between ACVRL1 and USP15 (Additional file 1: Figure S3D), which indicated that ACVRL1 can directly interact with both GPX2 and USP15 independently."
sparser
"On further exploration, we found that knockdown of USP15 did not affect the interaction between ACVRL1 and GPX2 (Additional file xref : Figure S3C); similarly, knockdown of GPX2 also did not affect the interaction between ACVRL1 and USP15 (Additional file xref : Figure S3D), which indicated that ACVRL1 can directly interact with both GPX2 and USP15 independently."
sparser
"To determine whether USP15 regulates CBX5 ubiquitination and, thus, affects its expression, we first used an anti-CBX5 antibody to precipitate CBX5 in control and hypoxic PASMCs and found USP15 in those immune precipitates ( xref ), indicating that USP15 can bind to CBX5 in PASMCs."
reach
"To determine whether USP15 regulates CBX5 ubiquitination and, thus, affects its expression, we first used an anti-CBX5 antibody to precipitate CBX5 in control and hypoxic PASMCs and found USP15 in those immune precipitates (Figure 5B), indicating that USP15 can bind to CBX5 in PASMCs."
reach
"On further exploration, we found that knockdown of USP15 did not affect the interaction between ACVRL1 and GPX2 (Additional file 1: Figure S3C); similarly, knockdown of GPX2 also did not affect the interaction between ACVRL1 and USP15 (Additional file 1: Figure S3D), which indicated that ACVRL1 can directly interact with both GPX2 and USP15 independently."
sparser
"On further exploration, we found that knockdown of USP15 did not affect the interaction between ACVRL1 and GPX2 (Additional file xref : Figure S3C); similarly, knockdown of GPX2 also did not affect the interaction between ACVRL1 and USP15 (Additional file xref : Figure S3D), which indicated that ACVRL1 can directly interact with both GPX2 and USP15 independently."
Bisphenol A affects USP15
4
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Bisphenol A increases the amount of USP15.
2
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Bisphenol A decreases the amount of USP15.
2
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USP15 affects mitoxantrone
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4
Mitoxantrone binds USP15. 4 / 4
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4
reach
"The crystal structure of the USP15-mitoxantrone complex revealed predominantly hydrophobic interactions between mitoxantrone and USP15 residues Tyr855, Gly856, Gly860, and His862, which are located near the catalytic Cys269 [245].2-DGIn cancer, 2-deoxy-d-glucose (2-DG) interferes with D-glucose metabolism to decrease its proliferation [246]."
USP15 affects cell migration
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4
USP15 affects cell growth
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3
1
USP15 affects UL12
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4
USP15 affects Tumor Microenvironment
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4
USP15 affects T cell activation
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4
USP15 affects Neoplasm Metastasis
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4
USP15 affects K48-
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4
reach
"Moreover, knockdown of USP15 increased the levels of K63-lined ubiquitinated RIG-I (Fig. 7D, lane 1 and lane 3) and phosphorylated IRF-3 (Fig. 8E, lane 1 and lane 3), whereas miR-26a induced K63-RIG-I and phosphorylated IRF-3 was largely abrogated in the setting of USP15 knockdown (Fig. 7D and E, lane 3 and lane 4)."
USP15 affects Cell Survival
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3
reach
"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."
UL12 affects USP15
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4
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."
E3_Ub_ligase affects USP15
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2
2
reach
"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."
ABHD11-AS1 affects USP15
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4
Folic acid affects USP15
3
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reach
"Finally, flow cytometry analysis was performed with FITC as the x-axis and PI (PE-A) as the y-axis.To investigate the specific role of USP15-overexpressing Exos on LPS-induced polarization of THP1-M0 cells, the following experimental procedures were conducted: Firstly, the USP15-overexpressing Exos were co-cultured with LPS-treated THP1-M0 cells to induce their polarization."
USP4 affects BRAP
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3
USP15 affects lymphangiogenesis
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3
USP15 activates lymphangiogenesis. 3 / 3
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3
reach
"In the current study, our results found that MFSD4A-AS1 functioned as ceRNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of VEGFA and VEGFC on the one hand; on the other hand, MFSD4A-AS1 further activated TGF-β signaling by sponging miR-30c-2-3p to relieve the repressive effect of miR-30c-2-3p on TGFBR2 and USP15, which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC."
reach
"Mechanistic dissection further revealed that MFSD4A-AS1 functioned as competing endogenous RNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of vascular endothelial growth factors A and C, and further activated transforming growth factor (TGF)-beta 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 gene expression
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3
USP15 affects degradation
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3
USP15 affects Vascular Remodeling
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3
USP15 affects TRAF6-BECN1
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3
USP15 affects RORgammat
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3
USP15 affects Protein Stability
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3
USP15 affects Parkinson Disease
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3
reach
"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 Lymphatic Metastasis
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3
USP15 activates Lymphatic Metastasis. 3 / 3
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3
reach
"Mechanistic dissection further revealed that MFSD4A-AS1 functioned as competing endogenous RNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of vascular endothelial growth factors A and C, and further activated transforming growth factor (TGF)-beta signaling by sponging miR-30c-2-3p that targeted TGFBR2 and USP15, both of which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC."
reach
"In the current study, our results found that MFSD4A-AS1 functioned as ceRNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of VEGFA and VEGFC on the one hand; on the other hand, MFSD4A-AS1 further activated TGF-β signaling by sponging miR-30c-2-3p to relieve the repressive effect of miR-30c-2-3p on TGFBR2 and USP15, which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC."
USP15 affects Glioblastoma
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2
USP15 activates Glioblastoma. 2 / 3
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USP15 affects FABPs
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3
reach
"It is also strongly supposed that FABPs and perilipins are deubiquitinated by USP15 and that their enhanced stability synergistically contributes to increased lipid accumulation and inflammation in the development of NAFLD/NASH.An FPC diet is used to induce features of metabolic and hepatic NASH characteristics."
USP15 affects CD44v6
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3
sparser
"For example, USP15 can deubiquitinate and stabilize the murine double minute 2 (MDM2) protein to hinder cancer cell survival, xref and it can deubiquitinate and suppress the activation of the ten-eleven translocation 2 (TET2) protein, thereby diminishing tumor immunogenicity. xref Additionally, USP15 can interact with sequestosome−1 (SQSTM1) to abolish the activation of ring finger protein 26 (RNF26), facilitating the release of diverse vesicles for fast transport and utilization of intracellular substances. xref A recent study has indicated an elevated expression of USP15 in HCC tumor tissues, revealing a close association with metastasis and poor prognosis. xref Thus, gaining a thorough understanding of this crucial modification implicated in the regulation of HCC progression could offer novel perspectives for cancer therapeutics."
reach
"Furthermore, Western blot demonstrated that overexpression of NKD1 in colon cancer HCT116 cells significantly reduced the expression of USP15, while knockdown of NKD1 in RKO cells evidently increased USP15 expression (Figure 9C), which implied that NKD1 prohibited the expression of USP15 in colon cancer cells."
BRAP affects USP4
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3
SiUSP15#1 affects USP15
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2
Receptor-activated SMAD affects USP15
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2
Phenylmercury acetate affects USP15
2
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Foci affects USP15
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2
Deoxynivalenol affects USP15
2
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Cobalt dichloride affects USP15
2
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Associated deubiquitinating enzyme Ubp12p affects USP15
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2
sparser
"As VHL targets hypoxia‐inducible transcription factor (HIF‐α) for degradation, VHL inactivation and HIF‐α activation were associated with the oncogenic driver. xref USP15 is a component of the COP9 signalosome complex (CSN), which is associated with VHL. xref , xref Therefore the interaction between USP15 and VHL requires intensive study in the future."
USP15 affects tumor immunity
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2
USP15 affects removal K1299-linked monoubiquitin
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2
USP15 affects receptor-activated SMAD
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2
USP15 affects perilipins
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2
reach
"It is also strongly supposed that FABPs and perilipins are deubiquitinated by USP15 and that their enhanced stability synergistically contributes to increased lipid accumulation and inflammation in the development of NAFLD/NASH.An FPC diet is used to induce features of metabolic and hepatic NASH characteristics."
USP15 affects interaction
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2
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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2
USP15 affects cell death
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2
USP15 activates cell death. 2 / 2
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2
reach
"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)."
sparser
"As VHL targets hypoxia‐inducible transcription factor (HIF‐α) for degradation, VHL inactivation and HIF‐α activation were associated with the oncogenic driver. xref USP15 is a component of the COP9 signalosome complex (CSN), which is associated with VHL. xref , xref Therefore the interaction between USP15 and VHL requires intensive study in the future."
USP15 affects U4 snRNP
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2
USP15 affects Th17 differentiation
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1
USP15 affects TNBC
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2
USP15 affects TGF-β/Smad
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2
USP15 affects TGF-β/SMAD2
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2
USP15 affects SEV-induced phosphorylation NF-kappaB subunit p65 IRF3
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2
USP15 affects Nucleus Pulposus
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2
USP15 affects NASH
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2
USP15 affects LUBAC-dependent TRIM25
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2
USP15 affects L-glutamine
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2
USP15 activates L-glutamine. 2 / 2
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2
USP15 affects Imatinib resistance cells
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2
eidos
"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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1
1
USP15 affects ISG
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2
USP15 affects Genomic Instability
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2
reach
"Researchers discovered that The expression of the deubiquitinating enzyme USP15 is upregulated in the livers of HFD-fed mice and in liver biopsy tissues from patients with NAFLD or NASH, whereas hepatocyte deletion of USP15 suppresses hepatic steatosis, inflammation, and fibrosis in a mouse model of NASH (133)."
USP15 affects Deubiquitinase
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2
USP15 affects DNA repair
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2
reach
"Subsequently, through a series of comprehensive gain and loss-of-function experiments, we have reaffirmed the positive correlation between BRCC3 protein expression and USP15, confirming the pivotal role of USP15 in modulating the multiplication, invasiveness, and migration of bladder cancer by regulating BRCC3 expression.Subsequently, to assess the interaction between USP15 and BRCC3, we conducted meticulous Co-IP experiments, conclusively demonstrating direct binding between the two proteins."
USP15 affects Adenocarcinoma of Lung
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1
1
USP15 affects 3-methylcholanthrene
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2
Subquinocin affects USP15
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2
SMAD7 affects E3_Ub_ligase
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1
1
reach
"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."
Proteasome affects USP15
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1
1
PRP-Exos affects USP15
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2
PR-619 affects USP15
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2
Nucleus Pulposus affects USP15
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2
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 ."
Interferon affects USP15
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2
FKBP5 affects Nucleus Pulposus, and USP15
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2
E3_Ub_ligase affects SMAD7, and USP15
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1
1
reach
"Subsequently, through a series of comprehensive gain and loss-of-function experiments, we have reaffirmed the positive correlation between BRCC3 protein expression and USP15, confirming the pivotal role of USP15 in modulating the multiplication, invasiveness, and migration of bladder cancer by regulating BRCC3 expression.Subsequently, to assess the interaction between USP15 and BRCC3, we conducted meticulous Co-IP experiments, conclusively demonstrating direct binding between the two proteins."
reach
"Together, USP15, downstream of activated BRAF/MAPK pathway, functions as the proteostatic controller of TBX3 and determines the ultimate abundance.Remarkably, induction of Usp15 expression by BRAF/MAPK could be instant and dramatic, so that its level was augmented in E16.5 embryonic thyroid from mPTC mice compared to that from wild-type mice (Fig. 4f and Supplementary Fig. 3c)."