β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression

Abstract

Summary: Orderly progressions of events in the cell division cycle are necessary to ensure the replication of DNA and cell division. Checkpoint systems allow the accurate execution of each cell-cycle phase. The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. Cyclin F has important functions in regulating the cell cycle during the G2 checkpoint; however, the mechanisms underlying the regulation of cyclin F are poorly understood. Here, we observe that cyclin F is regulated by proteolysis through β-TrCP. β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. This event is required to promote mitotic progression and favors the activation of a transcriptional program required for mitosis. : Mavrommati et al. identify how cyclin F is regulated during mitosis by proteolysis. Cyclin F is ubiquitylated by β-TrCP after phosphorylation by CKII on S704 within a TSGXXS degron. β-TrCP-mediated degradation of cyclin F favors timely mitotic progression through the control of a B-Myb transcriptional program. Keywords: F-box protein, cyclin F, β-TrCP, mitosis, cell cycle, ubiquitin, SCF, CRLs, CKII