Regulation of the Anaphase-promoting Complex by the Dual Specificity Phosphatase Human Cdc14a

Two forms of the anaphase-promoting complex (APC) mediate the degradation of critical cell cycle regulators. APC^Cdc20 promotes sister-chromatid separation by ubiquitinating securin, whereas APC ^Cdh1 ubiquitinates mitotic cyclins, allowing the exit from mitosis. Here we show that phosphorylation of human Cdh1 (hCdh1) by cyclin B-Cdc2 alters the conformation of hCdh1 and prevents it from activating APC. A human homologue of yeast Cdc14, human Cdc14a (hCdc14a), dephosphorylates hCdh1 and activates APC^Cdh1. In contrast, hCdc14a does not affect the activity of APC^Cdc20. hCdc14a is a major phosphatase for hCdh1 and localizes to centrosomes in HeLa cells. Therefore, hCdc14a may promote the activation of APC^Cdh1 and exit from mitosis in mammalian cells.