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

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.
Mesh Terms:
Cell Cycle, Cell Line, Tumor, Cyclins, E2F1 Transcription Factor, E2F2 Transcription Factor, E2F3 Transcription Factor, Epithelial Cells, Gene Expression Regulation, Genetic Fitness, HEK293 Cells, HeLa Cells, Humans, Mutation, Osteoblasts, Proteolysis, SKP Cullin F-Box Protein Ligases, Signal Transduction, Transcription, Genetic, Ubiquitination
Mol. Cell
Date: Dec. 20, 2018
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