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.
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.
Ceseña
Teresa I
TI
Cellular and Molecular Biology Program, Department of Obstetrics/Gynecology, University of Michigan, Ann Arbor 48109, USA.
Cardinaux
Jean-Rene
JR
Kwok
Roland
R
Schwartz
Jessica
J
D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D023081:CCAAT-Binding Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000502:physiology; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D023081:CCAAT-Binding Factor; D022763:CCAAT-Enhancer-Binding Protein-alpha; D018797:Cell Cycle Proteins; D013006:Growth Hormone; D051548:Histone Acetyltransferases; D008239:Lysine; D016760:Proto-Oncogene Proteins c-fos; D012694:Serine; D013912:Threonine; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor