Regulation of cyclin-dependent kinase activity during mitotic exit and maintenance of genome stability by p21, p27, and p107

摘要: To study the regulation of cyclin-dependent kinase (CDK) activity during mitotic exit in mammalian cells, we constructed murine cell lines that constitutively express a stabilized mutant cyclin A (cyclin A47). Even though A47 was expressed throughout mitosis and G1 its associated CDK inactivated after transition from metaphase to anaphase. Cyclin with both p21 p27 exit, implicating these proteins inactivation. However, fully inhibited M-to-G1 p21(-/-) p27(-/-) fibroblasts. Also, CDKs were not by phosphorylation at tyrosines. The protein responsible for inactivation p21/p27 null cells Rb family member, p107. p107 bound when absent, A47-CDK p107(-/-) Enforced expression lacking all three inhibitors induced rapid tetraploidization, indicative failure/endoreduplication. We concluded proteolysis constitute redundant pathways control A-CDK loss can cause genetic instability.