IndraLab

Statements

USP13 is phosphorylated. 21 / 21
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"As shown in xref , T196 was phosphorylated after DNA damage, and the T196A mutation inhibited USP13 phosphorylation after DNA damage."
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"Together, these results suggest that USP13 phosphorylation by ATM is important for its recruitment to DSBs, DDR and chemo sensitivity."
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"Next, we investigated how USP13 phosphorylation regulates its localization."
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"Here the authors report that phosphorylated USP13 deubiquitinates RAP80 after DNA damage, prompting recruitment to the break site."
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"Taken together, these results demonstrate that USP13 phosphorylation by ATM is important for USP13 recruitment to DSB sites following DNA damage and proper DDR."
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"Identification of USP13 Phosphorylation in Ovarian Cancer Cells by LC-MS-MS Analysis."
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"The activity, expression, and cellular localization of CK2 components could further impact USP13 phosphorylation in response to intrinsic or extrinsic cellular stresses in the tumor microenvironment."
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"Following DNA damage, phosphorylated USP13 by ATM is recruited to DNA damage sites to cleave the ubiquitin chains from more than three sites of RAP80 (K75, K90, and K112), releasing their restriction on the K63-linked ubiquitin chain, improving the focus formation of the RAP80-BRCA1 complex, and eventually facilitating DDR."
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"To further confirm these results, we generated site-specific antibody against p-Thr196 and examined the USP13 phosphorylation following DNA damage."
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"The anti-pT122 antibody specifically detected a phosphorylated USP13 in HeyA8 and COV318 expressing wild-type USP13, not T122A mutant USP13 ( xref C,D)."
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"A recent study suggested that DNA damage could induce the phosphorylation of USP13 by the ATM and then activated USP13 deubiquitinated RAP80 (K75, K90, and K112)."
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"An in vitro kinase assay indicated that WT-CLK3 but not CLK3-K186M was able to directly phosphorylate USP13 ( xref )."
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"However, the phospho-mutant of USP13 (T122A) showed a significantly down-regulated half-life time in HEK293T cells ( xref A,B)."
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"We then examined the physiological significance of USP13 phosphorylation by CLK3 at Y708. xref indicates that CLK3 knockdown in HuCCT1 cells strongly impaired the interaction of USP13 with c-Myc."
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"We found that following cisplatin treatment, USP13 is phosphorylated at SQ/TQ motifs (Fig. 5a and Supplementary Fig. 8a-b), which are consensus ATM or ATR phosphorylation sites33."
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"CHX chase assay revealed that the phosphorylated USP13 at Thr122 was more stable than the total USP13 in ovarian cancer cells ( xref C,D)."
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"CDC-like kinase 3 (CLK3) functions on serine/threonine- and tyrosine-containing substrates to directly phosphorylate USP13 and promote its binding to c-Myc."
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"We found that following cisplatin treatment, USP13 is phosphorylated at SQ/TQ motifs ( xref and xref ), which are consensus ATM or ATR phosphorylation sites xref ."
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rlimsp
"Next, we investigated how USP13 phosphorylation regulates its localization."
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"In conclusion, we identified CK2-mediated phosphorylation of USP13 in ovarian cancer."
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"Inhibition of the phosphorylation of USP13 downregulated USP13 protein stability and reduced the proliferation of ovarian cancer cells, which may lead to novel therapeutics targeting USP13 in USP13-amplified cancers."
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