Article: article from journal or magazin.
CCAAT/enhancer-binding protein (C/EBP) beta is acetylated at multiple lysines: acetylation of C/EBPbeta at lysine 39 modulates its ability to activate transcription.
Journal of Biological Chemistry
Publication types: In Vitro ; Journal Article
Transcription factor function can be modulated by post-translational modifications. Because the transcription factor CCAAT/enhancer-binding protein (C/EBP) beta associates with the nuclear coactivator p300, which contains acetyltransferase activity, acetylation of C/EBPbeta was examined to understand its regulation and function. C/EBPbeta is acetylated by acetyltransferases p300 and p300/CREB-binding protein associated factor. Endogenous C/EBPbeta in 3T3-F442A preadipocytes is also recognized by an acetyl-lysine-specific antibody. Analysis of truncations of C/EBPbeta and peptides based on C/EBPbeta sequences identified multiple lysines within C/EBPbeta that can be acetylated. Among these, a novel acetylation site at lysine 39 of C/EBPbeta was identified. Mutation of Lys-39 to arginine or alanine impairs its acetylation and the ability of C/EBPbeta to activate transcription at the promoters for C/EBPalpha and c-fos. Different C/EBPbeta-responsive promoters require different patterns of acetylated lysines in C/EBPbeta for transcription activation. Furthermore, C/EBPbeta acetylation was increased by growth hormone, and mutation of Lys-39 impaired growth hormone-stimulated c-fos promoter activation. These data suggest that acetylation of Lys-39 of C/EBPbeta, alone or in combination with acetylation at other lysines, may play a role in C/EBPbeta-mediated transcriptional activation.
3T3 Cells, Acetylation, Animals, CCAAT-Binding Factor/chemistry, CCAAT-Binding Factor/genetics, CCAAT-Enhancer-Binding Protein-alpha/genetics, Cell Cycle Proteins/metabolism, Growth Hormone/metabolism, Histone Acetyltransferases/metabolism, Humans, Lysine/metabolism, Mice, Mutagenesis, Site-Directed, Promoter Regions, Genetic/physiology, Protein Structure, Tertiary, Proto-Oncogene Proteins c-fos/genetics, Serine/metabolism, Threonine/metabolism, Transcription Factors/metabolism, Transcriptional Activation/physiology, p300-CBP Transcription Factors
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