TY - JOUR
T1 - Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors
AU - Giandomenico, Valeria
AU - Simonsson, Maria
AU - Grönroos, Eva
AU - Ericsson, Johan
PY - 2003/4
Y1 - 2003/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037378516&partnerID=8YFLogxK
U2 - 10.1128/MCB.23.7.2587-2599.2003
DO - 10.1128/MCB.23.7.2587-2599.2003
M3 - Article
C2 - 12640139
AN - SCOPUS:0037378516
SN - 0270-7306
VL - 23
SP - 2587
EP - 2599
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 7
ER -