Cyclin proteolysis and CDK inhibitors: two redundant pathways to maintain genome stability in mammalian cells.
Cyclin-dependent kinases (CDKs) are regulated by cyclin proteolysis and CDK inhibitors (CKIs) during mitotic exit and G(1) phase in yeast and Drosophila, and disruption of both regulatory pathways leads to genomic instability. Our study using mouse cell lines that constitutively express a stabilized mutant of cyclin A revealed that three CKIs, p21, p27, and Rb-related p107, are responsible for cyclin proteolysis-independent inactivation of CDK during mitotic exit and G(1). Enforced expression of cyclin A in the cells lacking all three CKIs induced rapid tetraploidization. Thus, the redundant pathways consisting of cyclin proteolysis and CKIs control CDK activity during mitotic exit and contribute to maintenance of genome stability in mammalian cells.
Chibazakura
Taku
T
Department of Bioscience, Tokyo University of Agriculture, Japan. taku@nodai.ac.jp
D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D042822:Genomic Instability; D051379:Mice; D011499:Protein Processing, Post-Translational
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases