Cdh1 degradation is mediated by APC/C-Cdh1 and SCF-Cdc4 in budding yeast.

Cdh1, a substrate-recognition subunit of anaphase-promoting complex/cyclosome (APC/C), is a tumor suppressor, and it is downregulated in various tumor cells in humans. APC/C-Cdh1 is activated from late M phase to G1 phase by antagonizing Cdk1-mediated inhibitory phosphorylation. However, how Cdh1 protein levels are properly regulated is ill-defined. Here we show that Cdh1 is degraded via APC/C-Cdh1 and Skp1-Cullin1-F-box (SCF)-Cdc4 in the budding yeast Saccharomyces cerevisiae. Cdh1 degradation was promoted by forced localization of Cdh1 into the nucleus, where APC/C and SCF are present. Cdk1 promoted APC/C-Cdh1-mediated Cdh1 degradation, whereas polo kinase Cdc5 elicited SCF-Cdc4-mediated degradation. Thus, Cdh1 degradation is controlled via multiple pathways.