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

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  • Sandra S Haenni
  • Paul O Hassa
  • Matthias Altmeyer
  • Monika Fey
  • Ralph Imhof
  • Michael O Hottiger
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.
OriginalsprogEngelsk
TidsskriftInternational Journal of Biochemistry & Cell Biology
Vol/bind40
Udgave nummer10
Sider (fra-til)2274-83
Antal sider10
ISSN1357-2725
DOI
StatusUdgivet - 2008
Eksternt udgivetJa

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