DNA-damage-responsive acetylation of pRb regulates binding to E2F-1

EMBO Rep. 2006 Feb;7(2):192-8. doi: 10.1038/sj.embor.7400591.

Abstract

The pRb (retinoblastoma protein) tumour suppressor protein has a crucial role in regulating the G1- to S-phase transition, and its phosphorylation by cyclin-dependent kinases is an established and important mechanism in controlling pRb activity. In addition, the targeted acetylation of lysine (K) residues 873/874 in the carboxy-terminal region of pRb located within a cyclin-dependent kinase-docking site hinders pRb phosphorylation and thereby retains pRb in an active state of growth suppression. Here, we report that the acetylation of pRb K873/874 occurs in response to DNA damage and that acetylation regulates the interaction between the C-terminal E2F-1-specific domain of pRb and E2F-1. These results define a new role for pRb acetylation in the DNA damage signalling pathway, and suggest that the interaction between pRb and E2F-1 is controlled by DNA-damage-dependent acetylation of pRb.

MeSH terms

  • Acetylation
  • Animals
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • DNA Damage*
  • E2F1 Transcription Factor / metabolism*
  • Etoposide / pharmacology
  • Fluorescent Dyes
  • Gene Expression Regulation
  • Humans
  • Indoles
  • Luciferases / metabolism
  • Mice
  • Models, Biological
  • NIH 3T3 Cells
  • Nuclear Proteins / metabolism
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Protein Structure, Tertiary
  • Retinoblastoma Protein / chemistry
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • Transfection

Substances

  • E2F1 Transcription Factor
  • Fluorescent Dyes
  • Indoles
  • Nuclear Proteins
  • Nucleic Acid Synthesis Inhibitors
  • Retinoblastoma Protein
  • DAPI
  • Etoposide
  • Luciferases