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 SREBF1gene.
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. The isoforms are SREBP-1a and -1c (ADD-1).
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. SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell.
^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". Cell75 (1): 187–97. doi:10.1016/S0092-8674(05)80095-9. PMID8402897.
^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". Genomics25 (3): 667–673. doi:10.1016/0888-7543(95)80009-B. PMID7759101.
^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. ISSN0890-9369. PMID8918891.
^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. ISSN0013-7227. PMID11713202.
^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. ISSN0964-6906. PMID11929849.
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. PMID11485982.
Kotzka J, Müller-Wieland D (2006). "Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance?". Expert Opin. Ther. Targets8 (2): 141–149. doi:10.1517/1472822.214.171.124. PMID15102555.
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 Foundation17 (1): 62–5. doi:10.1053/j.jrn.2006.10.009. PMID17198935.
Ferré P, Foufelle F (2007). "SREBP-1c transcription factor and lipid homeostasis: clinical perspective". Horm. Res.68 (2): 72–82. doi:10.1159/000100426. PMID17344645.
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. PMID8006035.
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. PMID8314806.
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. PMID8626610.
Miserez AR, Cao G, Probst LC, Hobbs HH (1997). "Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2)". Genomics40 (1): 31–40. doi:10.1006/geno.1996.4525. PMID9070916.
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". Structure6 (5): 661–672. doi:10.1016/S0969-2126(98)00067-7. PMID9634703.
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. PMID9651391.
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. PMID10224053.
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". Cell99 (7): 703–12. doi:10.1016/S0092-8674(00)81668-2. PMID10619424.
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. PMID10915800.
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. Cell6 (1): 77–86. doi:10.1016/S1097-2765(00)00009-5. PMID10949029.