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Sterol regulatory element-binding protein 1

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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]

SREBF1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSREBF1, SREBP-1c, SREBP1, bHLHd1, SREBP1a, sterol regulatory element binding transcription factor 1
External IDsOMIM: 184756; MGI: 107606; HomoloGene: 3079; GeneCards: SREBF1; OMA:SREBF1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6720

20787

Ensembl

ENSG00000072310

ENSMUSG00000020538

UniProt

P36956

Q9WTN3

RefSeq (mRNA)

NM_001005291
NM_004176
NM_001321096

NM_011480
NM_001313979
NM_001358314
NM_001358315

RefSeq (protein)

NP_001005291
NP_001308025
NP_004167

NP_001300908
NP_035610
NP_001345243
NP_001345244

Location (UCSC)Chr 17: 17.81 – 17.84 MbChr 11: 60.09 – 60.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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Main article: Sterol regulatory element-binding protein

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 (oligomer with ten subunits) 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-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

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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

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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

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SREBF1 has been shown to interact with:

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000072310 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020538 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. PMID 8402897. S2CID 2784016.
  6. ^ 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. PMID 7759101.
  7. ^ "Entrez Gene: SREBF1 sterol regulatory element binding transcription factor 1".
  8. ^ Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F (November 2004). "SREBP transcription factors: master regulators of lipid homeostasis". Biochimie. 86 (11): 839–848. doi:10.1016/j.biochi.2004.09.018. PMID 15589694.
  9. ^ a b c Xu X, So JS, Park JG, Lee AH (November 2013). "Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP". Seminars in Liver Disease. 33 (4): 301–311. doi:10.1055/s-0033-1358523. PMC 4035704. PMID 24222088.
  10. ^ Shimano H, Yahagi N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y, et al. (December 1999). "Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes". The Journal of Biological Chemistry. 274 (50): 35832–35839. doi:10.21037/hbsn.2016.11.08. PMC 5218901. PMID 10585467.
  11. ^ Li S, Brown MS, Goldstein JL (February 2010). "Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis". Proceedings of the National Academy of Sciences of the United States of America. 107 (8): 3441–3446. Bibcode:2010PNAS..107.3441L. doi:10.1073/pnas.0914798107. PMC 2840492. PMID 20133650.
  12. ^ a b Ferré 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. PMID 21029304. S2CID 23614683.
  13. ^ Bakan I, Laplante M (June 2012). "Connecting mTORC1 signaling to SREBP-1 activation". Current Opinion in Lipidology. 23 (3): 226–234. doi:10.1097/MOL.0b013e328352dd03. PMID 22449814. S2CID 19390378.
  14. ^ Ponugoti B, Kim DH, Xiao Z, Smith Z, Miao J, Zang M, et al. (October 2010). "SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism". The Journal of Biological Chemistry. 285 (44): 33959–33970. doi:10.1074/jbc.M110.122978. PMC 2962496. PMID 20817729.
  15. ^ Song Z, Xiaoli AM, Yang F (September 2018). "Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues". Nutrients. 10 (10): E1383. doi:10.3390/nu10101383. PMC 6213738. PMID 30274245.
  16. ^ Guo D, Bell EH, Mischel P, Chakravarti A (2014). "Targeting SREBP-1-driven lipid metabolism to treat cancer". Current Pharmaceutical Design. 20 (15): 2619–2626. doi:10.2174/13816128113199990486. PMC 4148912. PMID 23859617.
  17. ^ 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. PMID 30914315. S2CID 85532042.
  18. ^ Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R (November 1996). "SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein". Genes & Development. 10 (22): 2903–2911. doi:10.1101/gad.10.22.2903. PMID 8918891.
  19. ^ Lopez D, Shea-Eaton W, Sanchez MD, McLean MP (December 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. 142 (12): 5097–5106. doi:10.1210/endo.142.12.8523. PMID 11713202.
  20. ^ Lloyd DJ, Trembath RC, Shackleton S (April 2002). "A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies". Human Molecular Genetics. 11 (7): 769–777. doi:10.1093/hmg/11.7.769. PMID 11929849.
  21. ^ Lee YS, Lee HH, Park J, Yoo EJ, Glackin CA, Choi YI, et al. (December 2003). "Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional activity of ADD1/SREBP1c". Nucleic Acids Research. 31 (24): 7165–7174. doi:10.1093/nar/gkg934. PMC 291873. PMID 14654692.
  22. ^ a b Gorski JP, Price JL (2016). "Bone muscle crosstalk targets muscle regeneration pathway regulated by core circadian transcriptional repressors DEC1 and DEC2". BoneKEy Reports. 5: 850. doi:10.1038/bonekey.2016.80. PMC 5111231. PMID 27867498.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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