Functional relevance of novel p300-mediated lysine 314 and 315 acetylation of RelA/p65.
Nuclear factor kappaB (NF-kappaB) 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 alpha was affected by acetylation on these residues. Microarray analysis of these cells treated with TNFalpha 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-kappaB dependent gene expression.
Buerki
Christine
C
Institute of Veterinary Biochemistry and Molecular Biology, 8057 Zurich, Switzerland.
Rothgiesser
Karin M
KM
Valovka
Taras
T
Owen
Heather R
HR
Rehrauer
Hubert
H
Fey
Monika
M
Lane
William S
WS
Hottiger
Michael O
MO
D000107:Acetylation; D019943:Amino Acid Substitution; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D051996:Transcription Factor RelA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
D050882:CREB-Binding Protein; D008239:Lysine; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C498144:Rela protein, mouse