-TrCP and Casein Kinase III Mediated Degradation of Cyclin F Controls Timely Mitotic Entry

Abstract

Coordinated progressions of events in the cell cycle are necessary to ensure the replication of DNA and cell division. Checkpoint systems allow the accurate execution of each cell cycle phase. Cyclins are core components of the cell cycle, which master cell cycle transitions and checkpoint controls. The precise regulation of cyclin levels is fundamental to coordinate cell division with checkpoint control to avoid genome instability. Cyclin F has crucial roles in coordinating cell cycle events with checkpoint control at the G2/M transition, however, the mechanisms underlying cyclin F regulation are poorly understood. Here, we identify a novel mode of regulation of cyclin F by proteolysis through β-TrCP. βTrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by CKIIα and PLK1. The degradation of cyclin F by β-TrCP occurs at the G2/M transition and allows the initiation of the transcriptional programme required for mitosis entry.