Sterol regulatory element-binding transcription factor 1 (SREBF1) also known assterol regulatory element-binding protein 1 (SREBP-1) is aprotein that in humans is encoded by theSREBF1gene.[5][6]
This gene is located within theSmith–Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene.[7] The isoforms are SREBP-1a and SREBP-1c (the latter also called ADD-1). SREBP-1a is expressed in the intestine and spleen, whereas SREBP-1c is mainly expressed in liver, muscle, and fat (among other tissues).[citation needed]
The proteins encoded by this gene aretranscription factors that bind to a sequence in thepromoter of different genes, called sterol regulatory element-1 (SRE1). This element is a decamer (oligomer with ten subunits) flanking theLDL 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 andendoplasmic 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-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell.[8]
SREBP-1a and SREBP-1c are both encoded by the same gene, but aretranscribed by different promoters.[9] For animals in a fasted state, SREBP-1c expression is suppressed in the liver, but a high carbohydrate meal (by insulin release) strongly induces SREBP-1c expression.[9]
SREBP-1 plays a key role in the induction oflipogenesis by the liver.[10]mTORC1 is activated byinsulin (a hormone of nutrient abundance) leading to increased production of SREBP-1c, which facilitates storage of fatty acids (excess nutrients) astriglycerides.[11]
SREBP-1c regulates genes required for glucose metabolism and fatty acid and lipid production and its expression is induced by insulin.[12]Insulin-stimulated SREBP-1c increasesglycolysis by activation ofglucokinase enzyme, and increaseslipogenesis (conversion of carbohydrates into fatty acids).[12] Insulin stimulation of SREBP-1c is mediated byliver X receptor (LXR) andmTORC1.[13]
High blood levels of insulin due toinsulin resistance often leads tosteatosis in the liver because of SREBP-1 activation.[9] Suppression of SREBP-1c bysirtuin 1[14] or by other means[15] protects against development of fatty liver.
SREBP-1 is highly activated in cancers because tumor cells require lipids for cell membranes,second messengers, and energy.[16][17]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, et al. (October 1993). "SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene".Cell.75 (1):187–197.doi:10.1016/S0092-8674(05)80095-9.PMID8402897.S2CID2784016.
^Hua X, Wu J, Goldstein JL, Brown MS, Hobbs HH (February 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.PMID7759101.
^abFerré P, Foufelle F (October 2010). "Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c".Diabetes, Obesity & Metabolism. 12 Suppl 2 (Suppl 2):83–92.doi:10.1111/j.1463-1326.2010.01275.x.PMID21029304.S2CID23614683.
^Ezzeddini R, Taghikhani M, Somi MH, Samadi N, Rasaee MJ (May 2019). "Clinical importance of FASN in relation to HIF-1α and SREBP-1c in gastric adenocarcinoma".Life Sciences.224:169–176.doi:10.1016/j.lfs.2019.03.056.PMID30914315.S2CID85532042.
Kotzka J, Müller-Wieland D (April 2004). "Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance?".Expert Opinion on Therapeutic Targets.8 (2):141–149.doi:10.1517/14728222.8.2.141.PMID15102555.S2CID34317215.
Szolkiewicz M, Chmielewski M, Nogalska A, Stelmanska E, Swierczynski J, Rutkowski B (January 2007). "The potential role of sterol regulatory element binding protein transcription factors in renal injury".Journal of Renal Nutrition.17 (1):62–65.doi:10.1053/j.jrn.2006.10.009.PMID17198935.
Wang X, Sato R, Brown MS, Hua X, Goldstein JL (April 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.PMID8156598.S2CID44899129.
Miserez AR, Cao G, Probst LC, Hobbs HH (February 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.PMID9070916.
