Fizzy/Cell Division Cycle 20 Related Protein 1 (FZR1)

Activation of the anaphase-promoting complex (APC) is required for anaphase initiation and for exit from mitosis. Fang et al. (1998) showed that APC is activated during mitosis and G1 by 2 regulatory factors, CDC20 and HCDH1. These proteins directly bind to APC and activate its cyclin ubiquitination activity. CDC20 confers a strict destruction box (D box) dependence on APC, while HCDH1 shows a much more relaxed specificity for the D box. HCDH1 contains WD40 repeats and is more closely related to yeast CDH1/HCT1 and Xenopus and Drosophila fzr, with which it shows 36%, 96%, and 69% sequence identity, respectively. In HeLa cells, the HCDH1 protein levels remain constant during the cell cycle and may target specific substrates lacking the D box in G1, such as polo-like kinase, for ubiquitination.