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Cell Rep. 2018 Sep 25;24(13):3404-3412. doi: 10.1016/j.celrep.2018.08.076.

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

Author information

1
Cancer Research UK and Medical Research Council Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
2
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA; NYU Perlmutter Cancer Center, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA.
3
Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7FZ, UK.
4
Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
5
Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy.
6
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA; NYU Perlmutter Cancer Center, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University School of Medicine, 522 First Avenue, SRB 1107, New York, NY 10016, USA. Electronic address: michele.pagano@nyumc.org.
7
Cancer Research UK and Medical Research Council Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. Electronic address: vincenzo.dangiolella@oncology.ox.ac.uk.

Abstract

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.

KEYWORDS:

CKII; CRLs; F-box protein; SCF; cell cycle; cyclin F; mitosis; ubiquitin; β-TrCP

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