The SIRT2 deacetylase regulates autoacetylation of p300

Mol Cell. 2008 Nov 7;32(3):449-55. doi: 10.1016/j.molcel.2008.09.018.

Abstract

Autoacetylation of the p300 histone acetyltransferase controls the transition between VP16-mediated chromatin acetylation and preinitiation complex (PIC) assembly. Currently, it is unknown if and how autoacetylated p300 is deacetylated. We found that the NAD(+)-dependent histone deacetylase SIRT2 deacetylates p300 in vitro and in cells. SIRT2 deacetylates lysine residues in the catalytic domain of p300 and restores binding of p300 to the PIC. RNAi-mediated depletion or chemical inhibition of SIRT2 in cells results in accumulation of acetylated p300. The altered ac-p300/p300 ratio in SIRT2-depleted cells results in decreased p300 recruitment to an integrated VP16-responsive gene and inhibition of transcription. We conclude that p300 undergoes a dynamic cycle of autoacetylation and deacetylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Cell Nucleus / enzymology
  • Cytoplasm / enzymology
  • HeLa Cells
  • Homeostasis
  • Humans
  • Kinetics
  • Protein Processing, Post-Translational
  • Recombinant Proteins / metabolism
  • Sirtuin 2
  • Sirtuins / genetics
  • Sirtuins / physiology*
  • p300-CBP Transcription Factors / metabolism*

Substances

  • Recombinant Proteins
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • SIRT2 protein, human
  • Sirtuin 2
  • Sirtuins