Nucleic Acids Research Advance Access published online on February 7, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn003
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Molecular Biology |
Functional relevance of novel p300-mediated lysine 314 and 315 acetylation of RelA/p65
1Institute of Veterinary Biochemistry and Molecular Biology, 2Functional Genomics Center Zurich, University of Zurich, 8057 Zurich, Switzerland and 3Mass Spectrometry and Proteomics Resource Laboratory, FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA
*To whom correspondence should be addressed. Tel: +41 44 6355474; Fax: 41 44 6356840; Email: hottiger{at}vetbio.uzh.ch
Received September 25, 2007. Revised December 17, 2007. Accepted January 5, 2008.
Nuclear factor kappaB (NF-
B) plays an important role in the transcriptional regulation of genes involved in immunity and cell survival. We show here in vitro and in vivo acetylation of RelA/p65 by p300 on lysine 314 and 315, two novel acetylation sites. Additionally, we confirmed the acetylation on lysine 310 shown previously. Genetic complementation of RelA/p65–/– cells with wild type and non-acetylatable mutants of RelA/p65 (K314R and K315R) revealed that neither shuttling, DNA binding nor the induction of anti-apoptotic genes by tumor necrosis factor 
was affected by acetylation on these residues. Microarray analysis of these cells treated with TNF identified specific sets of genes differently regulated by wild type or acetylation-deficient mutants of RelA/p65. Specific genes were either stimulated or repressed by the acetylation-deficient mutants when compared to RelA/p65 wild type. These results support the hypothesis that site-specific p300-mediated acetylation of RelA/p65 regulates the specificity of NF-B dependent gene expression.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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