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Mol Cell. 2019 Jun 20;74(6):1264-1277.e7. doi: 10.1016/j.molcel.2019.04.010. Epub 2019 May 23.

Cyclin F Controls Cell-Cycle Transcriptional Outputs by Directing the Degradation of the Three Activator E2Fs.

Author information

1
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Perlmutter NYU Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
2
Program of Immunogenomics, The Rockefeller University, New York, NY 10065, USA.
3
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
4
Program of Immunogenomics, The Rockefeller University, New York, NY 10065, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA; Perlmutter NYU Cancer Center, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: michele.pagano@nyumc.org.

Abstract

E2F1, E2F2, and E2F3A, the three activators of the E2F family of transcription factors, are key regulators of the G1/S transition, promoting transcription of hundreds of genes critical for cell-cycle progression. We found that during late S and in G2, the degradation of all three activator E2Fs is controlled by cyclin F, the substrate receptor of 1 of 69 human SCF ubiquitin ligase complexes. E2F1, E2F2, and E2F3A interact with the cyclin box of cyclin F via their conserved N-terminal cyclin binding motifs. In the short term, E2F mutants unable to bind cyclin F remain stable throughout the cell cycle, induce unscheduled transcription in G2 and mitosis, and promote faster entry into the next S phase. However, in the long term, they impair cell fitness. We propose that by restricting E2F activity to the S phase, cyclin F controls one of the main and most critical transcriptional engines of the cell cycle.

KEYWORDS:

E2F1; E2F2; E2F3A; F-box proteins; RNA-seq; SCF ligases; cell cycle; cyclin F; retinoblastoma; ubiquitin

PMID:
31130363
PMCID:
PMC6588466
[Available on 2020-06-20]
DOI:
10.1016/j.molcel.2019.04.010

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