@article{e2ac0a883e54458eb8813fd4ee7e9fc8,
title = "Cyclin F Controls Cell-Cycle Transcriptional Outputs by Directing the Degradation of the Three Activator E2Fs",
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",
author = "Linda Clijsters and Claire Hoencamp and Calis, {Jorg J.A.} and Antonio Marzio and Handgraaf, {Shanna M.} and Cuitino, {Maria C.} and Rosenberg, {Brad R.} and Gustavo Leone and Michele Pagano",
note = "Funding Information: We are grateful to R. Wolthuis, B. Dynlacht, B. King, T. Lionnet, and W.F. Marzluff for reagents and advice. We thank J. DeCaprio, B. Dynlacht, N. Dyson, and D. Simoneschi for critically reading the manuscript. We thank NYU Langone{\textquoteright}s scientific core facilities, the Genome Technology Center for performing library preparation and RNA sequencing, the Cytometry and Cell Sorting Laboratory for flow cytometry assistance (both are supported by grant P30CA016087 from the NIH/National Cancer Institute ), and the Microscopy Laboratory for assistance. This work was funded by grants from the NIH ( GM57587 and CA76584 ) to M.P. and a Rubicon grant from the Netherlands Organisation for Scientific Research (NWO) to L.C. M.P. is an investigator with the Howard Hughes Medical Institute. Funding Information: We are grateful to R. Wolthuis, B. Dynlacht, B. King, T. Lionnet, and W.F. Marzluff for reagents and advice. We thank J. DeCaprio, B. Dynlacht, N. Dyson, and D. Simoneschi for critically reading the manuscript. We thank NYU Langone's scientific core facilities, the Genome Technology Center for performing library preparation and RNA sequencing, the Cytometry and Cell Sorting Laboratory for flow cytometry assistance (both are supported by grant P30CA016087 from the NIH/National Cancer Institute), and the Microscopy Laboratory for assistance. This work was funded by grants from the NIH (GM57587 and CA76584) to M.P. and a Rubicon grant from the Netherlands Organisation for Scientific Research (NWO) to L.C. M.P. is an investigator with the Howard Hughes Medical Institute. L.C. performed and planned all experiments and cowrote the manuscript. M.P. directed and coordinated the study, oversaw all results, and cowrote the manuscript. C.H. A.M. and S.M.H. helped with some experiments. J.J.A.C. and B.R.R. performed RNA-seq and related analyses. M.C.C. and G.L. provided conceptual advice. All authors discussed the results and commented on the manuscript. M.P. is a member of the scientific advisory boards of CullGen Inc. and Kymera Therapeutics and a consultant for BeyondSpring Pharmaceutical. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = jun,
day = "20",
doi = "10.1016/j.molcel.2019.04.010",
language = "English",
volume = "74",
pages = "1264--1277.e7",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}