Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors
2003 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 23, no 7, 2587-2599 p.Article in journal (Refereed) Published
Members of the SREBP family of transcription factors control cholesterol and lipid homeostasis and play important roles during adipocyte differentiation. The transcriptional activity of SREBPs is dependent on the coactivators p300 and CBP. We now present evidence that SREBPs are acetylated by the intrinsic acetyltransferase activity of p300 and CBP. In SREBP1a, the acetylated lysine residue resides in the DNA-binding domain of the protein. Coexpression with p300 dramatically increases the expression of both SREBP1a and SREBP2, and this effect is dependent on the acetyltransferase activity of p300, indicating that acetylation of SREBPs regulates their stability. Indeed, acetylation or mutation of the acetylated lysine residue in SREBP1a stabilizes the protein. We demonstrate that the acetylated residue in SREBP1a is also targeted by ubiquitination and that acetylation inhibits this process. Thus, our studies define acetylation-dependent stabilization of transcription factors as a novel mechanism for coactivators to regulate gene expression.
Place, publisher, year, edition, pages
2003. Vol. 23, no 7, 2587-2599 p.
Acetylation, Acetyltransferases/metabolism, Amino Acid Motifs/physiology, Animals, CCAAT-Enhancer-Binding Proteins/*metabolism, COS Cells, Cell Cycle Proteins/metabolism, Cell Line, Cell Nucleus/metabolism, Cyclic AMP Response Element-Binding Protein/metabolism, DNA/metabolism, DNA-Binding Proteins/*metabolism, Gene Expression, Hela Cells, Histone Acetyltransferases, Humans, Multigene Family, Protein Structure; Tertiary/physiology, Recombinant Fusion Proteins/genetics/metabolism, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2, Sterols/biosynthesis, Transcription Factors/*metabolism, Transfection, Ubiquitin/metabolism
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-10501DOI: 10.1128/MCB.23.7.2587-2599.2003PubMedID: 12640139OAI: oai:DiVA.org:uu-10501DiVA: diva2:38269