Chk1-mediated phosphorylation of Cdh1 promotes the SCF^βTRCP-dependent degradation of Cdh1 during S-phase and efficient cell-cycle progression.

ABSTRACT: APC/C^Cdh1 is a ubiquitin ligase with roles in numerous diverse processes, including control of cellular proliferation and multiple aspects of the DNA damage response. Precise regulation of APC/C^Cdh1 activity is central to efficient cell-cycle progression and cellular homeostasis. Here, we have identified Cdh1 as a direct substrate of the replication stress checkpoint effector kinase Chk1 and demonstrate that Chk1-mediated phosphorylation of Cdh1 contributes to its recognition by the SCF^βTRCP ubiquitin ligase, promotes efficient S-phase entry, and is important for cellular proliferation during otherwise unperturbed cell cycles. We also find that prolonged Chk1 activity in late S/G2 inhibits Cdh1 accumulation. In addition to promoting control of APC/C^Cdh

SUBMITTER: Pal D 

PROVIDER: S-EPMC7188793 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature