IndraLab

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USP1 activates CHEK1. 9 / 10
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"Given that USP1 positively regulates CHK1 stabilization (Fig. S3B), to further examine whether the regulation of BRD7 on CHK1 is dependent on USP1, we performed a rescue experiment and found that USP1 silencing reversed the increase in CHK1 level (Fig. 3B, lanes 3 versus 2 and 1; Fig. 3C, lanes 11 versus 6 and 1) and protein half-life of CHK1 (Fig. 3C, lanes 11–15 versus 6–10 and 1–5) caused by BRD7 knockdown."

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"Two E3 ligase complexes, CUL4A and DDB1 and CUL1 and FBXO6, have shown to be responsible for Chk1 polyubiquitination and degradation; whereas deubiquitinases (DUB), USP1 and USP7, have been reported to promote Chk1 stabilization."

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"It has been previously reported that deubiquitinase USP1 maintains both total and phosphorylated Chk1 level and that USP1 deletion promotes degradation of activated Chk1 in a DDB1 dependent manner."

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"USP1, highly expressed in GBM and particularly in cells positive for GSC-enrichment markers (CD133 or CD15), modulates the stability of ID1 and CHEK1, which are critical for DDR and stem cell maintenance."

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"This resulted from an apparent combination of reduced CHK1 mRNA expression and down-regulation of the deubiquitinase USP1 that can function to promote CHK1 protein stability [20]."

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"USP1 enhanced protein stability of the ID1 and CHEK1, important regulators of DNA damage response and stem cell maintenance (Lee et al., 2016)."

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"Finally, to ascertain if elements other than mono-Ub-FANCD2 participate in USP1 mediated CHK1 downregulation, we depleted USP1 in FA-C, FA-G and FA-D2 fibroblasts."

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"USP1 limits DDB1 dependent degradation of CHK1."

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"USP1 knockdown abrogated BRD7 silencing-induced CHK1 induction."