Functional relevance of novel p300-mediated lysine 314 and 315 acetylation of ReIA/p65

被引：82

作者：

Buerki, Christine ^{[1
]}

Rothgiesser, Karin M. ^{[1
]}

Valovka, Taras ^{[1
]}

Owen, Heather R. ^{[1
]}

Rehrauer, Hubert ^{[2
]}

Fey, Monika ^{[1
]}

Lane, William S. ^{[3
]}

Hottiger, Michael O. ^{[1
]}

机构：

[1] Univ Zurich, Inst Vet Biochem & Mol Biol, CH-8057 Zurich, Switzerland

[2] Univ Zurich, Funct Genom Ctr Zurich, CH-8057 Zurich, Switzerland

[3] Harvard Univ, Mass Spectrometry & Proteo Resource Lab, FAS Ctr Syst Biol, Cambridge, MA 02138 USA

来源：

NUCLEIC ACIDS RESEARCH | 2008年 / 36卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

D O I：

10.1093/nar/gkn003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nuclear factor kappaB (NF-kappa 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 alpha was affected by acetylation on these residues. Microarray analysis of these cells treated with TNF alpha 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-kappa B dependent gene expression.

引用

页码：1665 / 1680

页数：16

共 53 条

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