SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
- PMID: 8156598
- DOI: 10.1016/0092-8674(94)90234-8
SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
Abstract
Sterol regulatory element-binding protein 1 (SREBP-1), a member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) family of transcription factors, is synthesized as a 125 kd precursor that is attached to the nuclear envelope and endoplasmic reticulum. In sterol-depleted cells, the membrane-bound precursor is cleaved to generate a soluble NH2-terminal fragment (apparent molecular mass, 68 kd) that translocates to the nucleus. This fragment, which includes the bHLH-ZIP domain, activates transcription of the genes for the LDL receptor and HMG CoA synthase. Sterols inhibit the cleavage of SREBP-1, and the 68 kd nuclear form is rapidly catabolized, thereby reducing transcription. ALLN, an inhibitor of neutral cysteine proteases, blocks the breakdown of the 68 kd form and superinduces sterol-regulated genes. Sterol-regulated proteolysis of a membrane-bound transcription factor provides a novel mechanism by which transcription can be regulated by membrane lipids.
Comment in
-
Basic-helix-loop-helix transcription factor and sterol sensor in a single membrane-bound molecule.Cell. 1994 Apr 8;77(1):17-9. doi: 10.1016/0092-8674(94)90230-5. Cell. 1994. PMID: 8156593 Review. No abstract available.
Similar articles
-
Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element-binding protein-1 (SREBP-1).J Biol Chem. 1994 Jun 24;269(25):17267-73. J Biol Chem. 1994. PMID: 8006035
-
SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element.Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11603-7. doi: 10.1073/pnas.90.24.11603. Proc Natl Acad Sci U S A. 1993. PMID: 7903453 Free PMC article.
-
Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane.J Biol Chem. 1996 Apr 26;271(17):10379-84. doi: 10.1074/jbc.271.17.10379. J Biol Chem. 1996. PMID: 8626610
-
Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins.World J Gastroenterol. 2004 Nov 1;10(21):3081-7. doi: 10.3748/wjg.v10.i21.3081. World J Gastroenterol. 2004. PMID: 15457548 Free PMC article. Review.
-
Basic-helix-loop-helix transcription factor and sterol sensor in a single membrane-bound molecule.Cell. 1994 Apr 8;77(1):17-9. doi: 10.1016/0092-8674(94)90230-5. Cell. 1994. PMID: 8156593 Review. No abstract available.
Cited by
-
Metabolic coessentiality mapping identifies C12orf49 as a regulator of SREBP processing and cholesterol metabolism.Nat Metab. 2020 Jun;2(6):487-498. doi: 10.1038/s42255-020-0206-9. Epub 2020 Jun 1. Nat Metab. 2020. PMID: 32694732 Free PMC article.
-
The amyloid precursor protein intracellular domain-fe65 multiprotein complexes: a challenge to the amyloid hypothesis for Alzheimer's disease?Int J Alzheimers Dis. 2012;2012:353145. doi: 10.1155/2012/353145. Epub 2012 Feb 9. Int J Alzheimers Dis. 2012. PMID: 22506131 Free PMC article.
-
Maturation and activity of sterol regulatory element binding protein 1 is inhibited by acyl-CoA binding domain containing 3.PLoS One. 2012;7(11):e49906. doi: 10.1371/journal.pone.0049906. Epub 2012 Nov 14. PLoS One. 2012. PMID: 23166793 Free PMC article.
-
Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1.J Clin Invest. 2012 Jul;122(7):2417-27. doi: 10.1172/JCI61462. Epub 2012 Jun 11. J Clin Invest. 2012. PMID: 22684109 Free PMC article.
-
Inflammatory stress increases unmodified LDL uptake via LDL receptor: an alternative pathway for macrophage foam-cell formation.Inflamm Res. 2009 Nov;58(11):809-18. doi: 10.1007/s00011-009-0052-4. Epub 2009 Jun 17. Inflamm Res. 2009. PMID: 19533020
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials