Transcription factor function is often modulated by post-translational modifications. The transcription factor CCAAT/Enhancer Binding Protein p (C/EBPp), which participates in events such as adipogenesis and immune function, is modified by phosphorylation. Since C/EBPp associates with the co-activator p300, which contains acetyltransferase activity, we examined whether C/EBP(3 is acetylated as a step toward understanding its regulation and function. C/EBPp was found to be acetylated by p300 and P/CAF. Four lysines in C/EBPp have so far been identified as potential sites for acetylation, and when each was mutated to non-acetylatable arginine residues, acetylation was reduced compared to wildtype C/EBPp. This project will investigate the functional consequences of C/EBPp acetylation by determining the importance of acetylation sites for activation of C/EBPp target genes. Preliminary data indicate that mutations impair activation of several genes. Among these are genes implicated in adipogenesis, suggesting that acetylation of C/EBPp contributes to its adipogenic properties. In addition, this project will examine the role of C/EBPp acetylation, deacetylation or phosphorylation in regulation of the acetylation state and activity of C/EBPp, and in its coactivation by p300. These studies will provide insight into transcription mechanisms in general, and into functions of C/EBPp that may be relevant to obesity and immune disorders. ? ? ?
|Cesena, Teresa I; Cui, Tracy X; Subramanian, Lalitha et al. (2008) Acetylation and deacetylation regulate CCAAT/enhancer binding protein beta at K39 in mediating gene transcription. Mol Cell Endocrinol 289:94-101|
|Cesena, Teresa I; Cui, Tracy Xiao; Piwien-Pilipuk, Graciela et al. (2007) Multiple mechanisms of growth hormone-regulated gene transcription. Mol Genet Metab 90:126-33|
|Cesena, Teresa I; Cardinaux, Jean-Rene; Kwok, Roland et al. (2007) 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. J Biol Chem 282:956-67|