The Retinoblastoma (RB) Tumor Suppressor: Pushing Back against Genome Instability on Multiple Fronts

Int J Mol Sci. 2017 Aug 16;18(8):1776. doi: 10.3390/ijms18081776.

Abstract

The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression. Over the years, studies have shown that RB participates in multiple processes in addition to cell cycle control. Indeed, RB is known to interact with over 200 different proteins and likely exists in multiple complexes. RB, in some cases, acts through its interaction with E2F1, other members of the pocket protein family (p107 and p130), and/or chromatin remodelers and modifiers. RB is a tumor suppressor with important chromatin regulatory functions that affect genomic stability. These functions include the role of RB in DNA repair, telomere maintenance, chromosome condensation and cohesion, and silencing of repetitive regions. In this review we will discuss recent advances in RB biology related to RB, partner proteins, and their non-transcriptional functions fighting back against genomic instability.

Keywords: BRG1; DNA repair; E2F1; EZH2; Non-homologous end joining; SWI/SNF; Suv4-20H; chromatin remodeling; homologous recombination; repetitive sequences.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Repair*
  • E2F Transcription Factors / genetics
  • E2F Transcription Factors / metabolism
  • Gene Silencing*
  • Genomic Instability*
  • Humans
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Retinoblastoma-Like Protein p107 / genetics
  • Retinoblastoma-Like Protein p107 / metabolism
  • Retinoblastoma-Like Protein p130 / genetics
  • Retinoblastoma-Like Protein p130 / metabolism
  • Telomere Homeostasis*

Substances

  • E2F Transcription Factors
  • RBL1 protein, human
  • RBL2 protein, human
  • Retinoblastoma Protein
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130