Cytoplasmic E3 ubiquitin ligase CUL9 controls cell proliferation, senescence, apoptosis and genome integrity through p53.

ABSTRACT: CUL9 is a member of the cullin family of E3 ubiquitin ligases, and it localizes predominantly in the cytoplasm. Deletion of Cul9 in mice results in increased DNA damage, widespread aneuploidy, spontaneous tumor development, accelerated Eμ-Myc-induced lymphomagenesis and susceptibility to carcinogenesis. CUL9 binds to p53 and causes cell apoptosis when ectopically expressed. Whether the function of CUL9 in maintaining genomic integrity and suppressing tumorigenesis is linked to p53 has not been genetically tested. Here we report that deletion of CUL9 in human cells results in attenuated p21 induction and impaired cellular response to DNA damage. We show that disruption of Cul9-p53 binding in mouse embryo fibroblasts (MEFs) by a knock-in mutation in Cul9 (Δp53) increases S-phase cell populat

SUBMITTER: Li Z 

PROVIDER: S-EPMC5589481 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature