Proteasome-dependent degradation of human CDC25B phosphatase

The CDC25 dual specificity phosphatase is a universal cell cycle regulator. The evolutionary conservation of this enzyme from yeast to man bears witne ss to its major role in the control of cyclin-dependent kinases (CDK) activ ity that are central regulators of the cell cycle machinery. CDC25 phosphat ase both dephosphorylates and activates CDKs. Three human CDC25s have been identified. CDC25A is involved in the control of G1/S, and CDC25C at G2/M t hrought the activation of CDK1-cyclin B. The exact function of CDC25B howev er remains elusive. We have found that CDC25B is degraded by the proteasome pathway in vitro and in vivo. This degradation is dependent upon phosphory lation by the CDK1-cyclin A complex, but not by CDK1-cyclin B. Together wit h the observations of others made in yeast and mammals, our results suggest that CDC25B might act as a 'mitotic starter' triggering the activation of an auto-amplification loop before being degraded.