Identification of lysines 36 and 37 of PARP-2 as targets for acetylation and auto-ADP-ribosylation

Int J Biochem Cell Biol. 2008;40(10):2274-83. doi: 10.1016/j.biocel.2008.03.008. Epub 2008 Mar 16.


Poly-ADP-ribose polymerase-2 (PARP-2) was described to regulate cellular functions comprising DNA surveillance, inflammation and cell differentiation by co-regulating different transcription factors. Using an in vitro and in vivo approach, we identified PARP-2 as a new substrate for the histone acetyltransferases PCAF and GCN5L. Site directed mutagenesis indicated that lysines 36 and 37, located in the nuclear localization signal of PARP-2, are the main targets for PCAF and GCN5L activity in vitro. Interestingly, acetylation of the same two PARP-2 residues reduces the DNA binding and enzymatic activity of PARP-2. Finally, PARP-2 with mutated lysines 36 and 37 showed reduced auto-mono-ADP-ribosylation when compared to wild type PARP-2. Together, our results provide evidence that acetylation of PARP-2 is a key post-translational modification that may regulate DNA binding and consequently also the enzymatic activity of PARP-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adenosine Diphosphate Ribose / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • DNA / metabolism
  • Humans
  • Lysine / metabolism*
  • Mice
  • Molecular Sequence Data
  • Mutant Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / chemistry
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Binding
  • p300-CBP Transcription Factors / metabolism


  • BLOC1S1 protein, human
  • Mutant Proteins
  • Nerve Tissue Proteins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Adenosine Diphosphate Ribose
  • DNA
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Poly(ADP-ribose) Polymerases
  • Parp2 protein, mouse
  • Lysine