IndraLab

Statements

USP21 is phosphorylated. 26 / 26
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rlimsp
"Induction of ES cell differentiation promotes the Extracellular Signal-Regulated Kinase (ERK)-dependent phosphorylation of USP21 and its dissociation from NANOG, leading to NANOG degradation [65]."
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rlimsp
"These data prompted us to examine whether p38 kinase is involved in the HSV-1–induced USP21 phosphorylation."
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rlimsp
"Taken together, these data indicate that p38-mediated USP21 phosphorylation enhances the binding of USP21 to STING."
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rlimsp
"p38 inhibition provides anti–DNA virus immunity by regulation of USP21 phosphorylation and STING activation."
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rlimsp
"Physiologically, our data from FACS showed that intravenous injection of HSV-1 into mice significantly induced the phosphorylation of USP21 in blood cells, which was correlated with the phosphorylated p38 levels (Fig. 9 G)."
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rlimsp
"However, knockdown of p38 expression resulted in a significant reduction in the phosphorylation of USP21 under HSV-1 stimulation at the indicated time (Fig. 9 F)."
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rlimsp
"Collectively, these data indicated that p38 is a physiological kinase involved in HSV-1–induced USP21 phosphorylation."
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rlimsp
"USP21 phosphorylation strongly promotes its binding to STING, which leads to removal of K27/63-linked polyubiquitin chains from STING and blocks the recruitment of TBK1 and IRF3 to STING, thereby resulting in the inactivation of type I IFN signaling."
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rlimsp
"These findings demonstrate that USP21 is a negative regulator of antiviral immunity and highlight a novel regulatory mechanism that involves the p38-mediated phosphorylation of USP21."
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rlimsp
"We next aimed to identify the protein kinase that regulates USP21 phosphorylation under HSV-1 infection by screening a library of kinase inhibitors."
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rlimsp
"We found p38 MAPK inhibitor SB202190, but none of other inhibitors screened significantly inhibited the phosphorylation of USP21 induced by HSV-1 (Fig. 9 A and Table S3)."
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rlimsp
"Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses."
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rlimsp
"p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation."
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rlimsp
"The phosphorylated USP21 in turn binds to STING and hydrolyzes K27/K63-linked polyubiquitination on STING."
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rlimsp
"(A) Phosphorylation of USP21 was identified in MS assay which was performed in Fig. 6 A. (B) USP21 contains a putative SPP motif at the C terminus that is conserved in different species."
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rlimsp
"The mechanism by which the phosphorylated USP21 is recruited to perinuclear microsome remains to be investigated."
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rlimsp
"We found that DNA virus regulates host antiviral responses through phosphorylation of USP21 to negatively regulate STING function."
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rlimsp
"Our data indicate that phosphorylation of USP21 differently affects DNA and RNA virus signaling."
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rlimsp
"These data are also consistent with our data showing that phosphorylation of USP21 differentially regulates DNA and RNA virus induced gene expression (Fig. 7, G and J)."
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rlimsp
"These data collectively suggest that p38-mediated USP21 phosphorylation may play different roles in host defense against DNA and RNA virus infection."
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rlimsp
"Our data showed that treatment with λ-phosphatase completely blocked the recognition of USP21, which was purified from HEK293T cells, by p-S538 antibody (Fig. 8 A), suggesting that p-S538 antibody specifically recognized the phosphorylated USP21."
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rlimsp
"Moreover, we confirmed that p-S538 antibody could be used to detect the phosphorylation of endogenous USP21 by immunofluorescence (Fig. 8, B and C)."
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rlimsp
"Interestingly, we also noticed that the phosphorylated USP21 was mostly localized at the perinuclear microsome (Fig. 8 E), which is similar to the subcellular localization of STING."
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rlimsp
"Our data showed that HSV-1 infection induced a significant co-localization between the phosphorylated USP21 and STING at the perinuclear microsome (Fig. 8 F)."
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rlimsp
"This prompted us to detect the co-localization between the phosphorylated USP21 and STING in cells."
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rlimsp
"Our data showed that the phosphorylation of USP21 was significantly increased upon HSV-1 infection when examined by Western blotting and immunofluorescence (Fig. 8, D and E)."
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