Updated project metadata. Updated publication reference for PubMed record(s): 30257202. 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 and this event is required to promote mitotic progression and favours the activation of a transcriptional programme required for mitosis.