PKA AND MPF-ACTIVATED POLO-LIKE KINASE REGULATE ANAPHASE-PROMOTING COMPLEX ACTIVITY AND MITOSIS PROGRESSION

Ubiquitin-mediated proteolysis is the key to cell cycle control. Anaph ase-promoting complex/cyclosome (APC) is a ubiquitin ligase that targe ts cyclin B and factors regulating sister chromatid separation for pro teolysis by the proteasome and, consequently, regulates metaphase-anap hase transition and exit from mitosis. Here we report that Cdc2-cyclin B-activated Polo-like kinase (Plk) specifically phosphorylates at lea st three components of APC and activates APC to ubiquitinate cyclin B in the in vitro-reconstituted system. Conversely, protein kinase A (PK A) phosphorylates two subunits of APC but suppresses APC activity. PKA is superior to Plk in its regulation of APC, and Plk activity peaks w hereas PKA activity is falling at metaphase. These results indicate th at Plk and PKA regulate mitosis progression by controlling APC activit y.