Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a protein that in humans is encoded by the SREBF1 gene.[1][2]
This gene is located within the Smith-Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene.[3] The isoforms are SREBP-1a and -1c (ADD-1).
Function
The proteins encoded by this gene are transcription factors that bind to a sequence in the promoter of different genes, called sterol regulatory element-1 (SRE1). This element is a decamer flanking the LDL receptor gene and other genes involved in, for instance, sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family.
SREBP-1c regulates genes required for glucose metabolism and fatty acid and lipid production and its expression is regulated by insulin.[4] SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell.[5]
Interactions
SREBF1 has been shown to interact with TWIST2,[6] CREB-binding protein,[7] DAX1[8] and LMNA.[9]
See also
References
- ^ Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS (November 1993). "SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene". Cell 75 (1): 187–97. doi:10.1016/S0092-8674(05)80095-9. PMID 8402897.
- ^ Hua X, Wu J, Goldstein JL, Brown MS, Hobbs HH (June 1995). "Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13". Genomics 25 (3): 667–673. doi:10.1016/0888-7543(95)80009-B. PMID 7759101.
- ^ "Entrez Gene: SREBF1 sterol regulatory element binding transcription factor 1".
- ^ Ferré P, Foufelle F (October 2010). "Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c". Diabetes Obes Metab 12 (Suppl 2): 83–92. doi:10.1111/j.1463-1326.2010.01275.x. PMID 21029304.
- ^ Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F (November 2004). "SREBP transcription factors: master regulators of lipid homeostasis". Biochimie 86 (11): 839–48. doi:10.1016/j.biochi.2004.09.018. PMID 15589694.
- ^ Lee, Yun Sok; Lee Hyoung Ho; Park Jiyoung; Yoo Eung Jae; Glackin Carlotta A; Choi Young Il; Jeon Sung Ho; Seong Rho Hyun; Park Sang Dai; Kim Jae Bum (Dec 2003). "Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional activity of ADD1/SREBP1c". Nucleic Acids Res. (England) 31 (24): 7165–7174. doi:10.1093/nar/gkg934. PMC 291873. PMID 14654692.
- ^ Oliner, J D; Andresen J M; Hansen S K; Zhou S; Tjian R (November 1996). "SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein". Genes Dev. (UNITED STATES) 10 (22): 2903–2911. doi:10.1101/gad.10.22.2903. ISSN 0890-9369. PMID 8918891.
- ^ Lopez, D; Shea-Eaton W; Sanchez M D; McLean M P (Dec 2001). "DAX-1 represses the high-density lipoprotein receptor through interaction with positive regulators sterol regulatory element-binding protein-1a and steroidogenic factor-1". Endocrinology (United States) 142 (12): 5097–5106. doi:10.1210/en.142.12.5097. ISSN 0013-7227. PMID 11713202.
- ^ Lloyd, David J; Trembath Richard C; Shackleton Sue (April 2002). "A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies". Hum. Mol. Genet. (England) 11 (7): 769–777. doi:10.1093/hmg/11.7.769. ISSN 0964-6906. PMID 11929849.
Further reading
- Osborne TF (2001). "CREating a SCAP-less liver keeps SREBPs pinned in the ER membrane and prevents increased lipid synthesis in response to low cholesterol and high insulin". Genes Dev. 15 (15): 1873–1878. doi:10.1101/gad.916601. PMID 11485982.
- Kotzka J, Müller-Wieland D (2006). "Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance?". Expert Opin. Ther. Targets 8 (2): 141–149. doi:10.1517/14728222.8.2.141. PMID 15102555.
- Szolkiewicz M; Chmielewski M; Nogalska A et al. (2007). "The potential role of sterol regulatory element binding protein transcription factors in renal injury". Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation 17 (1): 62–5. doi:10.1053/j.jrn.2006.10.009. PMID 17198935.
- Ferré P, Foufelle F (2007). "SREBP-1c transcription factor and lipid homeostasis: clinical perspective". Horm. Res. 68 (2): 72–82. doi:10.1159/000100426. PMID 17344645.
- Hua X; Yokoyama C; Wu J et al. (1994). "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. 90 (24): 11603–7. doi:10.1073/pnas.90.24.11603. PMC 48032. PMID 7903453.
- Sato R; Yang J; Wang X et al. (1994). "Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element-binding protein-1 (SREBP-1)". J. Biol. Chem. 269 (25): 17267–73. PMID 8006035.
- Wang X; Sato R; Brown MS et al. (1994). "SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis". Cell 77 (1): 53–62. doi:10.1016/0092-8674(94)90234-8. PMID 8156598.
- Wang X; Briggs MR; Hua X et al. (1993). "Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. II. Purification and characterization". J. Biol. Chem. 268 (19): 14497–504. PMID 8314806.
- Hua X, Sakai J, Brown MS, Goldstein JL (1996). "Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane". J. Biol. Chem. 271 (17): 10379–10384. doi:10.1074/jbc.271.17.10379. PMID 8626610.
- Shimomura I; Shimano H; Horton JD et al. (1997). "Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells". J. Clin. Invest. 99 (5): 838–45. doi:10.1172/JCI119247. PMC 507890. PMID 9062340.
- Miserez AR, Cao G, Probst LC, Hobbs HH (1997). "Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2)". Genomics 40 (1): 31–40. doi:10.1006/geno.1996.4525. PMID 9070916.
- Párraga A, Bellsolell L, Ferré-D'Amaré AR, Burley SK (1998). "Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A resolution". Structure 6 (5): 661–672. doi:10.1016/S0969-2126(98)00067-7. PMID 9634703.
- Ericsson J, Edwards PA (1998). "CBP is required for sterol-regulated and sterol regulatory element-binding protein-regulated transcription". J. Biol. Chem. 273 (28): 17865–17870. doi:10.1074/jbc.273.28.17865. PMID 9651391.
- Bennett MK; Ngo TT; Athanikar JN et al. (1999). "Co-stimulation of promoter for low density lipoprotein receptor gene by sterol regulatory element-binding protein and Sp1 is specifically disrupted by the yin yang 1 protein". J. Biol. Chem. 274 (19): 13025–32. doi:10.1074/jbc.274.19.13025. PMID 10224053.
- Moldes M; Boizard M; Liepvre XL et al. (2000). "Functional antagonism between inhibitor of DNA binding (Id) and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP-1c) trans-factors for the regulation of fatty acid synthase promoter in adipocytes". Biochem. J. 344 (3): 873–80. doi:10.1042/0264-6021:3440873. PMC 1220711. PMID 10585876.
- DeBose-Boyd RA; Brown MS; Li WP et al. (2000). "Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi". Cell 99 (7): 703–12. doi:10.1016/S0092-8674(00)81668-2. PMID 10619424.
- Roth G; Kotzka J; Kremer L et al. (2000). "MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro". J. Biol. Chem. 275 (43): 33302–7. doi:10.1074/jbc.M005425200. PMID 10915800.
- Shimomura I; Matsuda M; Hammer RE et al. (2000). "Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice". Mol. Cell 6 (1): 77–86. doi:10.1016/S1097-2765(00)00009-5. PMID 10949029.
External links
- SREBF1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook SREBP1
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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