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Description

Fizzy-related protein homolog (UniProt: Q9R1K5, also known as Fzr, Cdh1/Hct1 homolog) is encoded by the Fzr1 (also known as Fyr, Fzr) gene (Gene ID: 56371) in murine species. Cdh1 is a substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex that associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. APC/C is activated upon sequential binding to the Cdc20 and Cdh1 adaptor proteins. Cdc20 associates with APC/C during early mitosis and principally regulates mitotic progression, while Cdh1 interacts with the APC/C from late mitosis onwards until the following G1/S transition. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition Cdh1 is phosphorylated, leading to its dissociation from the APC/C. It has been shown that Cdk-mediated Cdh1 phosphorylation prevents Cdh1 from associating with APC/C prematurely during S/G2 phase, while CDC14B phosphatase-dependent APC/C-Cdh1 activation in response to DNA damage during G2 phase leads to ubiquitination and degradation of Polo-like kinase 1 (Plk1) and prevents entry into mitosis. Following DNA repair, Cdk1 and Plk1 are reactivated and cell cycle progresses from G2 into mitosis phase.