Regulation of E2F1 Transcription Factor by Ubiquitin Conjugation

Laurence Dubrez

doi:10.3390/ijms18102188

Abstract

Ubiquitination is a post-translational modification that defines the cellular fate of intracellular proteins. It can modify their stability, their activity, their subcellular location, and even their interacting pattern. This modification is a reversible event whose implementation is easy and fast. It contributes to the rapid adaptation of the cells to physiological intracellular variations and to intracellular or environmental stresses. E2F1 (E2 promoter binding factor 1) transcription factor is a potent cell cycle regulator. It displays contradictory functions able to regulate both cell proliferation and cell death. Its expression and activity are tightly regulated over the course of the cell cycle progression and in response to genotoxic stress. I discuss here the most recent evidence demonstrating the role of ubiquitination in E2F1’s regulation.

Highlights

E2F1 (E2 promoter binding factor 1) is the founding member of an evolutionarily conserved family of transcription factors that play critical roles in the regulation of the cell cycle and apoptosis
In quiescent cells, gene promoters are occupied by the repressors E2F4 and E2F5, associated with the Rb-related pocket proteins p107 or p130, while E2F activators are inactivated by binding to Rb
The free E2F activators can initiate the transcription of E2F target genes, driving G1 to S phase transition while E2F4 and E2F5 are shuttled to the cytoplasm

Summary

Introduction

E2F1 (E2 promoter binding factor 1) is the founding member of an evolutionarily conserved family of transcription factors that play critical roles in the regulation of the cell cycle and apoptosis. The E2F–Rb interaction is dependent on the phosphorylation status of Rb. Other important partners are its co-factor, dimerization partner 1 (DP1), which is critical to the high-affinity binding of the transcription factors to DNA, and cyclin A, which is required for the cyclic regulation of E2F1 along the cell cycle. Other important partners are its co-factor, dimerization partner 1 (DP1), which is critical to the high-affinity binding of the transcription factors to DNA, and cyclin A, which is required for the cyclic regulation of E2F1 along the cell cycle Besides these three major regulators, a number of co-factors and co-regulators have been described; most of them are protein-modifying enzymes. This review will present an overview of the regulation of E2F1 by ubiquitin conjugation modifications

Ubiquitination

Cell Cycle Regulation of E2F1 by Ubiquitination

Conclusions