Title | Cyclin F Controls Cell-Cycle Transcriptional Outputs by Directing the Degradation of the Three Activator E2Fs. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Clijsters L, Hoencamp C, Calis JJA, Marzio A, Handgraaf SM, Cuitiño MC, Rosenberg BR, Leone G, Pagano M |
Journal | Mol Cell |
Volume | 74 |
Issue | 6 |
Pagination | 1264-1277.e7 |
Date Published | 2019 06 20 |
ISSN | 1097-4164 |
Keywords | 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, Signal Transduction, SKP Cullin F-Box Protein Ligases, Transcription, Genetic, Ubiquitination |
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. |
DOI | 10.1016/j.molcel.2019.04.010 |
Alternate Journal | Mol Cell |
PubMed ID | 31130363 |
PubMed Central ID | PMC6588466 |
Grant List | P30 CA016087 / CA / NCI NIH HHS / United States R01 GM057587 / GM / NIGMS NIH HHS / United States R01 CA121275 / CA / NCI NIH HHS / United States R01 CA076584 / CA / NCI NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States |
Related Lab:
Related Faculty:
Antonio Marzio, Ph.D.