Sterol regulatory element-binding protein 1
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 17: 17.81 – 17.84 Mb | Chr 11: 60.09 – 60.11 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
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.[5][6]
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.[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]
Expression
The proteins encoded by this gene are
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 are transcribed 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]
Function
SREBP-1 plays a key role in the induction of lipogenesis by the liver.[10] mTORC1 is activated by insulin (a hormone of nutrient abundance) leading to increased production of SREBP-1c, which facilitates storage of fatty acids (excess nutrients) as triglycerides.[11]
Clinical relevance
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 increases glycolysis by activation of glucokinase enzyme, and increases lipogenesis (conversion of carbohydrates into fatty acids).[12] Insulin stimulation of SREBP-1c is mediated by liver X receptor (LXR) and mTORC1.[13]
High blood levels of insulin due to insulin resistance often leads to steatosis in the liver because of SREBP-1 activation.[9] Suppression of SREBP-1c by sirtuin 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]
Interactions
SREBF1 has been shown to interact with:
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000072310 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020538 – Ensembl, May 2017
- ^ "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.
- S2CID 2784016.
- PMID 7759101.
- ^ "Entrez Gene: SREBF1 sterol regulatory element binding transcription factor 1".
- PMID 15589694.
- ^ PMID 24222088.
- PMID 10585467.
- PMID 20133650.
- ^ S2CID 23614683.
- S2CID 19390378.
- PMID 20817729.
- PMID 30274245.
- PMID 23859617.
- S2CID 85532042.
- PMID 8918891.
- PMID 11713202.
- PMID 11929849.
- PMID 14654692.
- ^ PMID 27867498. Retrieved 2017-04-13.
Further reading
- Osborne TF (Aug 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 & Development. 15 (15): 1873–8. PMID 11485982.
- Kotzka J, Müller-Wieland D (Apr 2004). "Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance?". Expert Opinion on Therapeutic Targets. 8 (2): 141–9. S2CID 34317215.
- Szolkiewicz M, Chmielewski M, Nogalska A, Stelmanska E, Swierczynski J, Rutkowski B (Jan 2007). "The potential role of sterol regulatory element binding protein transcription factors in renal injury". Journal of Renal Nutrition. 17 (1): 62–5. PMID 17198935.
- Ferré P, Foufelle F (2007). "SREBP-1c transcription factor and lipid homeostasis: clinical perspective". Hormone Research. 68 (2): 72–82. PMID 17344645.
- Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X (Dec 1993). "SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element". Proceedings of the National Academy of Sciences of the United States of America. 90 (24): 11603–7. PMID 7903453.
- Sato R, Yang J, Wang X, Evans MJ, Ho YK, Goldstein JL, Brown MS (Jun 1994). "Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element-binding protein-1 (SREBP-1)". The Journal of Biological Chemistry. 269 (25): 17267–73. PMID 8006035.
- Wang X, Sato R, Brown MS, Hua X, Goldstein JL (Apr 1994). "SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis". Cell. 77 (1): 53–62. S2CID 44899129.
- Wang X, Briggs MR, Hua X, Yokoyama C, Goldstein JL, Brown MS (Jul 1993). "Nuclear protein that binds sterol regulatory element of low density lipoprotein receptor promoter. II. Purification and characterization". The Journal of Biological Chemistry. 268 (19): 14497–504. PMID 8314806.
- Hua X, Sakai J, Brown MS, Goldstein JL (Apr 1996). "Regulated cleavage of sterol regulatory element binding proteins requires sequences on both sides of the endoplasmic reticulum membrane". The Journal of Biological Chemistry. 271 (17): 10379–84. PMID 8626610.
- Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS (Mar 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". The Journal of Clinical Investigation. 99 (5): 838–45. PMID 9062340.
- Miserez AR, Cao G, Probst LC, Hobbs HH (Feb 1997). "Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2)". Genomics. 40 (1): 31–40. PMID 9070916.
- Párraga A, Bellsolell L, Ferré-D'Amaré AR, Burley SK (May 1998). "Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A resolution". Structure. 6 (5): 661–72. PMID 9634703.
- Ericsson J, Edwards PA (Jul 1998). "CBP is required for sterol-regulated and sterol regulatory element-binding protein-regulated transcription". The Journal of Biological Chemistry. 273 (28): 17865–70. PMID 9651391.
- Bennett MK, Ngo TT, Athanikar JN, Rosenfeld JM, Osborne TF (May 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". The Journal of Biological Chemistry. 274 (19): 13025–32. PMID 10224053.
- Moldes M, Boizard M, Liepvre XL, Fève B, Dugail I, Pairault J (Dec 1999). "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". The Biochemical Journal. 344 Pt 3 (3): 873–80. PMID 10585876.
- DeBose-Boyd RA, Brown MS, Li WP, Nohturfft A, Goldstein JL, Espenshade PJ (Dec 1999). "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. PMID 10619424.
- Roth G, Kotzka J, Kremer L, Lehr S, Lohaus C, Meyer HE, Krone W, Müller-Wieland D (Oct 2000). "MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro". The Journal of Biological Chemistry. 275 (43): 33302–7. PMID 10915800.
- Shimomura I, Matsuda M, Hammer RE, Bashmakov Y, Brown MS, Goldstein JL (Jul 2000). "Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice". Molecular Cell. 6 (1): 77–86. PMID 10949029.
External links
- SREBF1+protein,+human at the U.S. 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.
PDB gallery | |
|---|---|
|
