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Beschreibung

Fizzy-related protein homolog (UniProt Q9UM11, also known as CDC20-like protein 1, Cdh1/Hct1 homolog, hCDH1, Fzr) is encoded by the FZR1 (also known as CDH1, FYR, FZR, KIAA1242) gene (Gene ID 51343) in human. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase involved in cell cycle regulation. 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. DNA-end resection factor CtIP. 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 Polo-like kinase 1 (Plk1) degradation. Following DNA double-strand breaks (DSB) repair, Cdk1 and Plk1 are reactivated to allow cell cycle progression from G2 into mitosis. Cdh1-depleted cells or Cdh1 / mice exhibit elevated levels of DNA damage and chromosomal aberrations. APC/C-Cdh1 interacts with the KEN box motif on its target proteins and known APC/C-Cdh1 substrates include the the de-SUMOylation enzyme SENP2, and and the fragile X syndrome protein FMRP.