Role for cyclin-dependent kinase 2 in mitosis exit.

Journal article

Mitosis requires cyclin-dependent kinase (cdk) 1-cyclin B activity [1]. Exit from mitosis depends on the inactivation of the complex by the degradation of cyclin B [2]. Cdk2 is also active during mitosis [3, 4]. In Xenopus egg extracts, cdk2 is primarily in complex with cyclin E, which is stable [5]. At the end of mitosis, downregulation of cdk2-cyclin E activity is accompanied by inhibitory phosphorylation of cdk2 [6]. Here, we show that cdk2-cyclin E activity maintains cdk1-cyclin B during mitosis. At mitosis exit, cdk2 is inactivated prior to cdk1. The loss of cdk2 activity follows and depends upon an increase in protein kinase A (PKA) activity. Prematurely inactivating cdk2 advances the time of cyclin B degradation and cdk1 inactivation. Blocking PKA, instead, stabilizes cdk2 activity and inhibits cyclin B degradation and cdk1 inactivation. The stabilization of cdk1-cyclin B is also induced by a mutant cdk2-cyclin E complex that is resistant to inhibitory phosphorylation. P21-Cip1, which inhibits both wild-type and mutant cdk2-cyclin E, reverses mitotic arrest under either condition. Our findings indicate that the proteolysis-independent downregulation of cdk2 activity at the end of mitosis depends on PKA and is required to activate the proteolysis cascade that leads to mitosis exit.

Authors: D'Angiolella, V; Costanzo, V; Gottesman, M; Avvedimento, E; Gautier, J

• Publication status: Published
• Journal: Current biology : CB
• Volume: 11
• Issue: 15
• Pages: 1221-1226
• Publication date: 2001-08-01
• DOI: 10.1016/s0960-9822(01)00352-9
• EISSN: 1879-0445
• ISSN: 0960-9822
• Language: English
• Keywords: Cyclin-Dependent Kinase 2; CDC2-CDC28 Kinases; Cyclin-Dependent Kinases; Protein-Serine-Threonine Kinases; Animals; Xenopus Proteins; Mitosis; Xenopus