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

Overview

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.

publication date

  • May 23, 2019

Research

keywords

  • Cell Cycle
  • Cyclins
  • E2F1 Transcription Factor
  • E2F2 Transcription Factor
  • E2F3 Transcription Factor
  • SKP Cullin F-Box Protein Ligases
  • Transcription, Genetic

Identity

PubMed Central ID

  • PMC6588466

Scopus Document Identifier

  • 85067232482

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2019.04.010

PubMed ID

  • 31130363

Additional Document Info

volume

  • 74

issue

  • 6