Coactivator-dependent Acetylation Stabilizes Members of the SREBP Family of Transcription Factors

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2003 Mar 18

PMID 12640139

Citations 107

Authors

Valeria Giandomenico

Maria Simonsson

Eva Gronroos

Johan Ericsson

Affiliations

Soon will be listed here.

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.

Citing Articles

SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis.

Shi L, Chen H, Zhang Y, An D, Qin M, Yu W EMBO J. 2025; 44(5):1442-1463.

PMID: 39824985 PMC: 11876347. DOI: 10.1038/s44318-025-00362-y.

Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.

Yang Y, Liao J, Pan Z, Meng J, Zhang L, Shi W Adv Sci (Weinh). 2024; 12(5):e2413103.

PMID: 39656925 PMC: 11791979. DOI: 10.1002/advs.202413103.

Roles of posttranslational modifications in lipid metabolism and cancer progression.

Feng T, Zhang H, Zhou Y, Zhu Y, Shi S, Li K Biomark Res. 2024; 12(1):141.

PMID: 39551780 PMC: 11571667. DOI: 10.1186/s40364-024-00681-y.

Identification of Potential New Genes Related to the SREBP Pathway in .

Venegas M, Duran A, Campusano S, Barahona S, Sepulveda D, Baeza M Biomolecules. 2024; 14(7).

PMID: 39062491 PMC: 11274570. DOI: 10.3390/biom14070778.

Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy.

Jafari M, Macho-Gonzalez A, Diaz A, Lindenau K, Santiago-Fernandez O, Zeng M Proc Natl Acad Sci U S A. 2024; 121(26):e2317945121.

PMID: 38889154 PMC: 11214046. DOI: 10.1073/pnas.2317945121.

References

Foretz M, Guichard C, Ferre P, Foufelle F . Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes. Proc Natl Acad Sci U S A. 1999; 96(22):12737-42. PMC: 23076. DOI: 10.1073/pnas.96.22.12737. View

Naar A, Beaurang P, Robinson K, Oliner J, Avizonis D, Scheek S . Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro. Genes Dev. 1998; 12(19):3020-31. PMC: 317191. DOI: 10.1101/gad.12.19.3020. View

Sartorelli V, Puri P, Hamamori Y, Ogryzko V, Chung G, Nakatani Y . Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program. Mol Cell. 2000; 4(5):725-34. DOI: 10.1016/s1097-2765(00)80383-4. View

Suzuki T, Kimura A, Nagai R, Horikoshi M . Regulation of interaction of the acetyltransferase region of p300 and the DNA-binding domain of Sp1 on and through DNA binding. Genes Cells. 2000; 5(1):29-41. DOI: 10.1046/j.1365-2443.2000.00302.x. View

Cardinaux J, Notis J, Zhang Q, Vo N, Craig J, Fass D . Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation. Mol Cell Biol. 2000; 20(5):1546-52. PMC: 85336. DOI: 10.1128/MCB.20.5.1546-1552.2000. View

Martinez-Balbas M, Bauer U, Nielsen S, Brehm A, Kouzarides T . Regulation of E2F1 activity by acetylation. EMBO J. 2000; 19(4):662-71. PMC: 305604. DOI: 10.1093/emboj/19.4.662. View

Kouzarides T . Acetylation: a regulatory modification to rival phosphorylation?. EMBO J. 2000; 19(6):1176-9. PMC: 305658. DOI: 10.1093/emboj/19.6.1176. View

Waltzer L, Bienz M . Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature. 1998; 395(6701):521-5. DOI: 10.1038/26785. View

Grossman S, Perez M, Kung A, Joseph M, Mansur C, Xiao Z . p300/MDM2 complexes participate in MDM2-mediated p53 degradation. Mol Cell. 1998; 2(4):405-15. DOI: 10.1016/s1097-2765(00)80140-9. View

10.

Munshi N, Merika M, Yie J, Senger K, Chen G, Thanos D . Acetylation of HMG I(Y) by CBP turns off IFN beta expression by disrupting the enhanceosome. Mol Cell. 1998; 2(4):457-67. DOI: 10.1016/s1097-2765(00)80145-8. View

11.

Boyes J, Byfield P, Nakatani Y, Ogryzko V . Regulation of activity of the transcription factor GATA-1 by acetylation. Nature. 1998; 396(6711):594-8. DOI: 10.1038/25166. View

12.

Naar A, Beaurang P, Zhou S, Abraham S, SOLOMON W, Tjian R . Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature. 1999; 398(6730):828-32. DOI: 10.1038/19789. View

13.

Cockell M, Gasser S . Nuclear compartments and gene regulation. Curr Opin Genet Dev. 1999; 9(2):199-205. DOI: 10.1016/S0959-437X(99)80030-6. View

14.

Chen H, Lin R, Xie W, Wilpitz D, Evans R . Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell. 1999; 98(5):675-86. DOI: 10.1016/s0092-8674(00)80054-9. View

15.

Nishihara A, Hanai J, Imamura T, Miyazono K, Kawabata M . E1A inhibits transforming growth factor-beta signaling through binding to Smad proteins. J Biol Chem. 1999; 274(40):28716-23. DOI: 10.1074/jbc.274.40.28716. View

16.

Brown M, Goldstein J . A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci U S A. 1999; 96(20):11041-8. PMC: 34238. DOI: 10.1073/pnas.96.20.11041. View

17.

Parraga A, Bellsolell L, Ferre-DAmare A, Burley S . Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A resolution. Structure. 1998; 6(5):661-72. DOI: 10.1016/s0969-2126(98)00067-7. View

18.

Sakai J, Rawson R, Espenshade P, Cheng D, Seegmiller A, Goldstein J . Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells. Mol Cell. 1998; 2(4):505-14. DOI: 10.1016/s1097-2765(00)80150-1. View

19.

Bannister A, Miska E, Gorlich D, Kouzarides T . Acetylation of importin-alpha nuclear import factors by CBP/p300. Curr Biol. 2000; 10(8):467-70. DOI: 10.1016/s0960-9822(00)00445-0. View

20.

Rosen E, Walkey C, Puigserver P, Spiegelman B . Transcriptional regulation of adipogenesis. Genes Dev. 2000; 14(11):1293-307. View