Sterol regulatory element-binding protein 2 explained

Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the SREBF2 gene.^[1]

Function

This gene encodes a ubiquitously expressed transcription factor that controls cholesterol homeostasis by stimulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix leucine zipper (bHLH-Zip) domain.^[2] Various single nucleotide polymorphisms (SNPs) of the SREBF2 have been identified and some of them are found to be associated with higher risk of knee osteoarthritis. ^[3]

Interactions

SREBF2 has been shown to interact with INSIG1^{[4] [5]} and CREB-binding protein.^[6]

See also

• Sterol regulatory element-binding protein

Further reading

• Osborne TF . 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 . Aug 2001 . 11485982 . 10.1101/gad.916601 . free .
• Szolkiewicz M, Chmielewski M, Nogalska A, Stelmanska E, Swierczynski J, Rutkowski B . The potential role of sterol regulatory element binding protein transcription factors in renal injury . Journal of Renal Nutrition . 17 . 1 . 62–5 . Jan 2007 . 17198935 . 10.1053/j.jrn.2006.10.009 .
• Hua X, Wu J, Goldstein JL, Brown MS, Hobbs HH . 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 . 667–73 . Feb 1995 . 7759101 . 10.1016/0888-7543(95)80009-B .
• Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS . 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 . Oct 1993 . 8402897 . 10.1016/S0092-8674(05)80095-9 . 2784016 .
• Wang X, Zelenski NG, Yang J, Sakai J, Brown MS, Goldstein JL . Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis . The EMBO Journal . 15 . 5 . 1012–20 . Mar 1996 . 8605870 . 449996 . 10.1002/j.1460-2075.1996.tb00438.x.
• Hua X, Sakai J, Brown MS, Goldstein JL . 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 . Apr 1996 . 8626610 . 10.1074/jbc.271.17.10379 . free .
• Pai JT, Brown MS, Goldstein JL . Purification and cDNA cloning of a second apoptosis-related cysteine protease that cleaves and activates sterol regulatory element binding proteins . Proceedings of the National Academy of Sciences of the United States of America . 93 . 11 . 5437–42 . May 1996 . 8643593 . 39264 . 10.1073/pnas.93.11.5437 . 1996PNAS...93.5437P . free .
• Sato R, Inoue J, Kawabe Y, Kodama T, Takano T, Maeda M . Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2 . The Journal of Biological Chemistry . 271 . 43 . 26461–4 . Oct 1996 . 8900111 . 10.1074/jbc.271.43.26461 . free .
• Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R . SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein . Genes & Development . 10 . 22 . 2903–11 . Nov 1996 . 8918891 . 10.1101/gad.10.22.2903 . free .
• Miserez AR, Cao G, Probst LC, Hobbs HH . Structure of the human gene encoding sterol regulatory element binding protein 2 (SREBF2) . Genomics . 40 . 1 . 31–40 . Feb 1997 . 9070916 . 10.1006/geno.1996.4525 .
• Duncan EA, Brown MS, Goldstein JL, Sakai J . Cleavage site for sterol-regulated protease localized to a leu-Ser bond in the lumenal loop of sterol regulatory element-binding protein-2 . The Journal of Biological Chemistry . 272 . 19 . 12778–85 . May 1997 . 9139737 . 10.1074/jbc.272.19.12778 . free .
• Harris IR, Farrell AM, Holleran WM, Jackson S, Grunfeld C, Elias PM, Feingold KR . Parallel regulation of sterol regulatory element binding protein-2 and the enzymes of cholesterol and fatty acid synthesis but not ceramide synthesis in cultured human keratinocytes and murine epidermis . Journal of Lipid Research . 39 . 2 . 412–22 . Feb 1998 . 10.1016/S0022-2275(20)33902-X . 9508001 . free .
• Kan HY, Pissios P, Chambaz J, Zannis VI . DNA binding specificity and transactivation properties of SREBP-2 bound to multiple sites on the human apoA-II promoter . Nucleic Acids Research . 27 . 4 . 1104–17 . Feb 1999 . 9927745 . 148292 . 10.1093/nar/27.4.1104 .
• Seidah NG, Mowla SJ, Hamelin J, Mamarbachi AM, Benjannet S, Touré BB, Basak A, Munzer JS, Marcinkiewicz J, Zhong M, Barale JC, Lazure C, Murphy RA, Chrétien M, Marcinkiewicz M . Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization . Proceedings of the National Academy of Sciences of the United States of America . 96 . 4 . 1321–6 . Feb 1999 . 9990022 . 15461 . 10.1073/pnas.96.4.1321 . 1999PNAS...96.1321S . free .
• Nagoshi E, Imamoto N, Sato R, Yoneda Y . Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip . Molecular Biology of the Cell . 10 . 7 . 2221–33 . Jul 1999 . 10397761 . 25438 . 10.1091/mbc.10.7.2221 .
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–95 . Dec 1999 . 10591208 . 10.1038/990031 . 1999Natur.402..489D . free .
• DeBose-Boyd RA, Brown MS, Li WP, Nohturfft A, Goldstein JL, Espenshade PJ . 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 . Dec 1999 . 10619424 . 10.1016/S0092-8674(00)81668-2 . free .
• Kotzka J, Müller-Wieland D, Roth G, Kremer L, Munck M, Schürmann S, Knebel B, Krone W . Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade . Journal of Lipid Research . 41 . 1 . 99–108 . Jan 2000 . 10.1016/S0022-2275(20)32079-4 . 10627507 . free .
• Yang T, Goldstein JL, Brown MS . Overexpression of membrane domain of SCAP prevents sterols from inhibiting SCAP.SREBP exit from endoplasmic reticulum . The Journal of Biological Chemistry . 275 . 38 . 29881–6 . Sep 2000 . 10896675 . 10.1074/jbc.M005439200 . free .

Notes and References

1. Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X . 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 . Dec 1993 . 7903453 . 48032 . 10.1073/pnas.90.24.11603 . 1993PNAS...9011603H . free .
2. Web site: Entrez Gene: SREBF2 sterol regulatory element binding transcription factor 2.
3. Qiu XM, Jin CT, Wang W . Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population . The Journal of International Medical Research . 42 . 2 . 320–8 . Apr 2014 . 24496149 . 10.1177/0300060513507392 . free .
4. Dobrosotskaya IY, Goldstein JL, Brown MS, Rawson RB . Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs . The Journal of Biological Chemistry . 278 . 37 . 35837–43 . Sep 2003 . 12842885 . 10.1074/jbc.M306476200 . free .
5. Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS . Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER . Cell . 110 . 4 . 489–500 . Aug 2002 . 12202038 . 10.1016/S0092-8674(02)00872-3 . 15052132 . free .
6. Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R . SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein . Genes & Development . 10 . 22 . 2903–11 . Nov 1996 . 8918891 . 10.1101/gad.10.22.2903 . free .