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Cyclin F Controls Cell-Cycle Transcriptional Outputs By Directing The Degradation Of The Three Activator E2Fs.
L. Clijsters, Claire Hoencamp, Jorg J. A. Calis, Antonio Marzio, Shanna M Handgraaf, M. Cuitiño, B. Rosenberg, G. Leone, M. Pagano
Published 2019 · Biology, Medicine
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Email 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.
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