Regulation of APC activity by phosphorylation and regulatory factors

Ubiquitin-dependent proteolysis of Cut2/Pds1 and Cyclin B is required for s ister chromatid separation and exit from mitosis, respectively. Anaphase-pr omoting complex/cyclosome (APC) specifically ubiquitinates Cut2/Pds1 at met aphase-anaphase transition, and ubiquitinates Cyclin B in late mitosis and G1 phase. However, the exact regulatory mechanism of substrate-specific act ivation of mammalian APC with the right timing remains to be elucidated. We found that not only the binding of the activators Cdc20 and Cdh1 and the i nhibitor Mad2 to APC, but also the phosphorylation of Cdc20 and Cdh1 by Cdc 2-Cyclin B and that of APC by Polo-like kinase and cAMP-dependent protein k inase, regulate APC activity. The cooperation of the phosphorylation/dephos phorylation and the regulatory factors in regulation of APC activity may th us control the precise progression of mitosis.