Cans C, Ducommun B, Baldin V
Institut de Pharmacologie et de Biologie Structurale du CNRS and Université Paul Sabatier, Toulouse, France.
Mol Biol Rep. 1999 Apr;26(1-2):53-7. doi: 10.1023/a:1006912105352.
The CDC25 dual specificity phosphatase is a universal cell cycle regulator. The evolutionary conservation of this enzyme from yeast to man bears witness to its major role in the control of cyclin-dependent kinases (CDK) activity that are central regulators of the cell cycle machinery. CDC25 phosphatase 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 throught the activation of CDK 1-cyclin B. The exact function of CDC25B however remains elusive. We have found that CDC25B is degraded by the proteasome pathway in vitro and in vivo. This degradation is dependent upon phosphorylation by the CDK1-cyclin A complex, but not by CDK1-cyclin B. Together with 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.
细胞周期蛋白依赖性激酶25（CDC25）双特异性磷酸酶是一种普遍的细胞周期调节因子。这种酶从酵母到人类的进化保守性证明了其在控制细胞周期蛋白依赖性激酶（CDK）活性中的主要作用，而CDK是细胞周期机制的核心调节因子。CDC25磷酸酶既能使CDK去磷酸化，又能激活CDK。已鉴定出三种人类CDC25。CDC25A参与G1/S期的调控，而CDC25C通过激活CDK1-细胞周期蛋白B参与G2/M期的调控。然而，CDC25B的确切功能仍不清楚。我们发现，CDC25B在体外和体内均可通过蛋白酶体途径降解。这种降解依赖于CDK1-细胞周期蛋白A复合物的磷酸化作用，而不依赖于CDK1-细胞周期蛋白B的磷酸化作用。与其他在酵母和哺乳动物中所做的观察结果一起，我们的结果表明，CDC25B可能作为一个“有丝分裂启动器”，在被降解之前触发一个自放大环的激活。
