Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors

Valeria Giandomenico, Maria Simonsson, Eva Grönroos, Johan Ericsson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

203 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2587-2599
Number of pages13
JournalMolecular and Cellular Biology
Volume23
Issue number7
DOIs
Publication statusPublished - Apr 2003
Externally publishedYes

Fingerprint

Dive into the research topics of 'Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors'. Together they form a unique fingerprint.

Cite this