ROLE OF INHIBITORY PHOSPHORYLATION OF CYCLIN A-Cdk 1 ON MITOTIC PROGRESSION

概要

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Exit from mitosis requires inactivation of Cdk1 primarily by ubiquitin-dependent proteolysis of mitotic cyclins (A2, B1 and B3) and overexpression of non-degradable cyclins inhibits mitotic progression. However, their stable expression at the endogenous cyclin level did not cause such an effect, indicating an additional mechanism (s) for suppression of Cdk1 activity. We induced the mutations at potential phosphorylation sites of Cdk1 for generation of cyclin A2-Cdk1 fusion genes as models of cyclin A2-Cdk1 complex. The product of the wild-type Cdk1 fusion gene had the Km values for hisotne H1 and lamin B similar to those of the natural mitotic cyclins-Cdk1 complex. Ectopic expression of cyclin A2-Cdk1 caused slightly delay of mitotic progression, whereas expression of its phosphorylation-deficient mutants inhibited mitotic progression. Stable expression of the mutant caused phenotypic change of the cells to multinucleation, suggesting the prolonged impairment of mitotic exit. Our findings demonstrated that phosphorylation of Cdk1 causes its inactivation and is prerequisite for proper mitotic exit as its additional regulation mechanism to the proteolytic degradation.
名古屋市立大学の論文
2007-02-28