IndraLab

Statements

USP15 is phosphorylated. 59 / 59
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sparser
"As expected, the effect of purvalanol A was similar to those of the phosphomutants, indicating that CDKs could be a possible candidate responsible for USP15 phosphorylation."
31330151
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"Finally, USP15 is phosphorylated by ATR/ATM and is known to cleave ubiquitin from IκB, thus dampening the NF-κB response (see below)."
19489724
rlimsp
"Mechanisms to control USP15 activity within cells are suggested by evidence that USP15 is alternatively spliced [18, 35] and can be ubiquitylated or phosphorylated [29, 34, 36–39]."
29429988
sparser
"Using the UALCAN database, we studied the expression of USP15 phosphorylation in breast cancer and normal tissues."
36213818
sparser
"The expression of phosphorylated USP15 in breast cancer tissues was higher than that in normal tissues. ( p = 6.87e − 04) ( xref ), the phosphorylation expression of USP15 in different stages of breast cancer was also analyzed."
36213818
rlimsp
"(B and C) Phosphorylated forms of both REST (B) and USP15 (C) accumulate during prometaphase arrest."
23708518
sparser
"Mechanisms to control USP15 activity within cells are suggested by evidence that USP15 is alternatively spliced [ xref , xref ] and can be ubiquitylated or phosphorylated [ xref , xref , xref – xref ]."
29429988
sparser
"USP15 is phosphorylated during HSV-1 infection."
40824090
rlimsp
"USP15 phosphorylation is essential for its functions in HR."
30874560
sparser
"To investigate the phosphorylation-dependent regulation of USP15, we first examined whether USP15 was phosphorylated in cells."
31330151
sparser
"Moreover, USP15 is phosphorylated during the cell cycle to regulate the mitotic degradation of the RE1-silencing transcription factor (REST) and subsequently dephosphorylated in early G1 while REST is stabilized and re-accumulated [ xref ]."
32512887
sparser
"Finally, we observed that USP15 is phosphorylated early during infection, and the phosphorylation is independent of ATM or DNA synthesis."
40824090
sparser
"In addition, Flag-USP15 was co-precipitated efficiently by pS/pT antibody affinity purification ( Fig. 1 c), which further confirms the phosphorylation of USP15 in cells."
31330151
sparser
"To further assess the consequence of USP15 phosphorylation in cells, we attempted to identify the specific phosphorylation sites based on its localization."
31330151
sparser
"In BRCA, several databases, including GEPIA and UALCAN, describe the upregulation of total protein levels and USP15 phosphorylation."
36213818
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"Next, we investigated whether the USP15 phosphorylation mediated changes in localization are dependent on SART3 by co-expressing SART3 with USP15."
31330151
sparser
"These data identified that AKT mediated phosphorylation of USP15 regulated autophagy in MPP + -induced PD models."
40441471
sparser
"HSV-1 DNA replication activates the ATM kinase, so we hypothesized that USP15 would be phosphorylated during infection."
40824090
sparser
"These results indicate that the phosphorylation of USP15 regulates its interaction with SART3, which induces its accumulation in the nucleus."
31330151
sparser
"Indeed, we observed phosphorylation of USP15 as early as 2 hours post-infection by mobility shift in SDS-PAGE."
40824090
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"The observations of the altered interactions between SART3 and the phosphorylated USP15 at positions T149 and T219 prompted us to analyze the deubiquitinating activity toward PRP31 in the spliceosome."
31330151
sparser
"Next, we searched for a potential kinase of USP15 phosphorylation."
31330151
rlimsp
"USP15 increases in abundance and becomes phosphorylated at the start of mitosis, coinciding with mitotic degradation of REST."
29429988
rlimsp
"No phospho-SQ/TQ signal was detected in Atm-deficient mouse embryonic fibroblasts (MEFs) (Fig. 4b), suggesting that USP15 is phosphorylated in an ATM-dependent manner."
30874560
rlimsp
"As pervasive mitotic phosphorylation often inactivates protein functions [37], USP15 phosphorylation may abrogate its role in stabilising REST at mitosis, allowing REST to degrade."
29429988
sparser
"Surprisingly, neither an HSV DNA replication inhibitor nor a specific ATM inhibitor prevented the phosphorylation of USP15."
40824090
rlimsp
"Interestingly, we observed that a proportion of USP15 became phosphorylated at mitosis, which could conceivably alter its activity toward REST."
23708518
sparser
"These results suggest that the non-phosphorylated USP15, as a result of CDK inhibition, is predominantly localized in the nucleus."
31330151
sparser
"To test whether DNA replication was required for phosphorylation of USP15, we infected Vero cells with KOS in the presence of the viral helicase/primase inhibitor or a selective ATM inhibitor."
40824090
sparser
"It should be noted that in addition to the interaction with SART3, the misregulation of phosphorylation of USP15 could be closely related to diseases."
31330151
sparser
"These data suggest that DNA replication is not required to phosphorylate USP15 and that there is an additional kinase involved."
40824090
sparser
"This interaction between USP15 and RIPK1 is regulated by phosphorylation of specific sites on USP15, which enhances its binding to RIPK1 and promotes the stabilization of RIPK1."
38030604
rlimsp
"To examine how USP15 phosphorylation affects cellular sensitivity to DNA damage, we reconstituted USP15-KO cells with ectopically expressed WT USP15 or USP15 S678A mutant."
30874560
rlimsp
"Thus, ATM-dependent USP15 phosphorylation has two effects: (1) affecting the sub-cellular localization of USP15, and (2) affecting the recruitment of USP15 to DSBs."
30874560
sparser
"Nevertheless, further studies are needed to elucidate the regulation of RNA splicing according to the cell cycle by reversible phosphorylation of USP15 or USP4."
31330151
sparser
"USP15 phosphorylation is essential for its functions in HR."
30874560
sparser
"To examine how USP15 phosphorylation affects cellular sensitivity to DNA damage, we reconstituted USP15-KO cells with ectopically expressed WT USP15 or USP15 S678A mutant."
30874560
rlimsp
"f Phosphorylated USP15 co-localizes with MDC1 upon DNA damage."
30874560
sparser
"Future work will determine whether phosphorylation of USP15 is required to stabilize UL12 and promote recombination."
40824090
sparser
"We further showed that the phosphorylation of both USP15 and USP4 is regulated by the activity of CDKs, although a question remains on which CDK, or whether more than one CDK, is required for this pho[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
31330151
sparser
"Since UL12 is required for the nuclear localization of USP15 during infection, we hypothesized that UL12 might be required for USP15 phosphorylation."
40824090
sparser
"Despite the lower expression due to the gD promoter, lentivirus-delivered UL12 was able to fully rescue the phosphorylation of USP15 during infection with AN-1."
40824090
sparser
"We observed that USP15 was phosphorylated in the presence of either inhibitor ( xref )."
40824090
rlimsp
"We next wanted to figure out whether USP15 phosphorylation affects its localization in cells."
30874560
sparser
"No phospho-SQ/TQ signal was detected in Atm -deficient mouse embryonic fibroblasts (MEFs) (Fig.  xref ), suggesting that USP15 is phosphorylated in an ATM-dependent manner."
30874560
sparser
"Since ATM is activated during KOS infection ( xref xref xref ) and USP15 is required for efficient HSV DNA replication, we hypothesized that USP15 would also be phosphorylated."
40824090
sparser
"However, as it is shown here, inhibition of USP15 phosphorylation by curcumin in HeLa cell lysates caused the formation of high-molecular-weight USP15 species, most likely USP15-Ub conjugates ( Figure[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16005295
rlimsp
"We noticed that USP15 levels accumulate along with REST during G2; however, prometaphase arrest disengaged their correlation (Fig. 6A) co-incident with the appearance of a phosphorylated form of USP15 that persisted during mitosis (Fig. 6C)."
23708518
sparser
"A recent study showed that the differential phosphorylation of USP15 on the UBL region (Thr149 and Thr219) results in an altered interaction with SART3 that affects USP15 localization and activity toward its substrate [ xref ]."
33946990
sparser
"CDK inhibitors prevent the expression of immediate early and early genes during HSV-1 infection ( xref ); therefore, it is not possible to see whether they prevent USP15 phosphorylation as UL12 expression is required."
40824090
rlimsp
"We previously showed that a proportion of USP15 is phosphorylated at mitosis [34], so we selectively depleted each isoform to establish whether they are differentially phosphorylated."
29429988
rlimsp
"The phosphorylation status of USP15 at these two positions alters the interaction with its partner protein SART3, consequently leading to its nuclear localization and deubiquitinating activity toward the substrate PRP31."
31330151
rlimsp
"Phosphorylation of USP15 and USP4 Regulates Localization and Spliceosomal Deubiquitination."
31330151
rlimsp
"Here, we show that USP15 is phosphorylated, and its localization and activity are dependent on the phosphorylation status."
31330151
sparser
"We next wanted to figure out whether USP15 phosphorylation affects its localization in cells."
30874560
sparser
"The phosphorylated USP15 was recruited to DSBs (Fig.  xref and Supplementary Fig.  xref ), while the S678A mutant, which abolished its phosphorylation by ATM, could not be recruited to DSBs (Fig.  xref )."
30874560
sparser
"We also cannot exclude the possibility that USP15 is phosphorylated by one of the HSV-1-encoded kinases."
40824090
sparser
"As pervasive mitotic phosphorylation often inactivates protein functions [ xref ], USP15 phosphorylation may abrogate its role in stabilising REST at mitosis, allowing REST to degrade."
29429988
sparser
"We also found that MDC1-FHA domain bound phosphorylated USP15, and Ser678 phosphorylation was essential for this binding (Fig.  xref )."
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