Identification of lysines 36 and 37 of PARP-2 as targets for acetylation and auto-ADP-ribosylation.
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.
Haenni
Sandra S
SS
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Hassa
Paul O
PO
Altmeyer
Matthias
M
Fey
Monika
M
Imhof
Ralph
R
Hottiger
Michael O
MO
D000107:Acetylation; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D000246:Adenosine Diphosphate Ribose; D004247:DNA; D008239:Lysine; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C104378:BLOC1S1 protein, human; C459820:Parp2 protein, mouse