Biology:NRIP1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example
Nuclear receptor-interacting protein 1 repression 1
Identifiers
SymbolNRIP1_repr_1
PfamPF15687
Nuclear receptor-interacting protein 1 repression 2
Identifiers
SymbolNRIP1_repr_2
PfamPF15688
Nuclear receptor-interacting protein 1 repression 3
Identifiers
SymbolNRIP1_repr_3
PfamPF15689
Nuclear receptor-interacting protein 1 repression 4
Identifiers
SymbolNRIP1_repr_4
PfamPF15690

Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.[1][2]

Function

Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors. Also known as RIP140, this protein is a key regulator which modulates transcriptional activity of a variety of transcription factors, including the estrogen receptor.[3]

RIP140 has an important role in regulating lipid and glucose metabolism,[4] and regulates gene expression in metabolic tissues including heart,[5] skeletal muscle,[6] and liver.[7] A major role for RIP140 in adipose tissue is to block the expression of genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1 and carnitine palmitoyltransferase 1b.[8]

Estrogen-related receptor alpha (ERRa) can activate RIP140 during adipogenesis, by means of directly binding to an estrogen receptor element/ERR element and indirectly through Sp1 binding to the proximal promoter.[9]

RIP140 suppresses the expression of mitochondrial proteins succinate dehydrogenase complex b and CoxVb and acts as a negative regulator of glucose uptake in mice.[10]

Knockout studies

Knockout mice that completely lack the RIP140 molecule are lean and stay lean, even on a rich diet.[11]

Knockout mice (females) are also infertile because they fail to ovulate.[12] Failure of ovulation in these mice is caused by lack of cumulus expansion and altered expression of various genes, including amphiregulin, in ovarian follicles.[13][14]

Clinical significance

RIP140 is part of the chain by which tumors can cause cachexia.[15][16]

Levels of RIP140 expression in various tissues varies during aging in mice, suggesting changes in metabolic function.[17] RIP140 is implicated in certain human disease processes. In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue.[18] In breast cancer, RIP140 is involved in regulation of E2F1, an oncogene which discriminates between luminal and basal types of tumours. RIP140 has an influence upon cancer phenotype and prognosis.[19] In addition, RIP140 has a role in inflammation, since it acts as a coactivator for NFkappaB/RelA-dependent cytokine gene expression. Lack of RIP140 leads to an inhibition of proinflammatory pathways in macrophages.[20]

Interactions

NRIP1 has been shown to interact with:


See also

References

  1. ↑ 1.0 1.1 "Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor". EMBO J 14 (15): 3741–51. Sep 1995. doi:10.1002/j.1460-2075.1995.tb00044.x. PMID 7641693. 
  2. ↑ "Localisation of receptor interacting protein 140 (RIP140) within 100 kb of D21S13 on 21q11, a gene-poor region of the human genome". Hum Genet 102 (2): 221–3. Apr 1998. doi:10.1007/s004390050682. PMID 9521594. 
  3. ↑ "Entrez Gene: NRIP1 nuclear receptor interacting protein 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8204. 
  4. ↑ "Role of nuclear receptor corepressor RIP140 in metabolic syndrome.". Biochim Biophys Acta 1812 (8): 919–28. 2010. doi:10.1016/j.bbadis.2010.12.016. PMID 21193034. 
  5. ↑ "Elevated expression of the metabolic regulator receptor-interacting protein 140 results in cardiac hypertrophy and impaired cardiac function.". Cardiovasc Res 86 (3): 443–451. 2010. doi:10.1093/cvr/cvp418. PMID 20083575. 
  6. ↑ "The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle". Cell Metab 6 (3): 236–245. Sep 2007. doi:10.1016/j.cmet.2007.08.004. PMID 17767910. 
  7. ↑ "The nuclear receptor cofactor, receptor-interacting protein 140, is required for the regulation of hepatic lipid and glucose metabolism by liver X receptor". Mol Endocrinol 21 (11): 2687–97. Nov 2007. doi:10.1210/me.2007-0213. PMID 17684114. 
  8. ↑ "Receptor interacting protein 140 regulates expression of uncoupling protein 1 in adipocytes through specific peroxisome proliferator activated receptor isoforms and estrogen-related receptor alpha". Mol. Endocrinol. 21 (7): 1581–92. July 2007. doi:10.1210/me.2007-0103. PMID 17456798. 
  9. ↑ "RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis.". J Biol Chem 281 (43): 32140–32147. Oct 2006. doi:10.1074/jbc.M604803200. PMID 16923809. 
  10. ↑ "Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes.". J Clin Invest 116 (1): 125–136. 2006. doi:10.1172/JCI26040. PMID 16374519. 
  11. ↑ "Nuclear receptor corepressor RIP140 regulates fat accumulation". Proc Natl Acad Sci U S A 101 (22): 8437–42. May 2004. doi:10.1073/pnas.0401013101. PMID 15155905. Bibcode: 2004PNAS..101.8437L. 
  12. ↑ "The nuclear receptor co-repressor nrip1 (RIP140) is essential for female fertility". Nat. Med. 6 (12): 1368–74. Dec 2000. doi:10.1038/82183. PMID 11100122. 
  13. ↑ "Multiple Signaling Defects in the Absence of RIP140 Impair Both Cumulus Expansion and Follicle Rupture". Endocrinology 146 (9): 4127–4137. 2005. doi:10.1210/EN.2005-0348. PMID 15919748. 
  14. ↑ "The nuclear receptor cofactor receptor-interacting protein 140 is a positive regulator of amphiregulin expression and cumulus cell-oocyte complex expansion in the mouse ovary". Endocrinology 151 (6): 2923–2932. 2010. doi:10.1210/en.2010-0081. PMID 20308529. 
  15. ↑ "A common denominator of inflammations and fatty liver". News. Science Centric. 2008-05-31. http://www.sciencecentric.com/news/article.php?q=08052824.  [|permanent dead link|dead link}}]
  16. ↑ "Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice". Hepatology 48 (3): 782–791. April 2008. doi:10.1002/hep.22383. PMID 18712775. 
  17. ↑ "Tissue-specific expression of receptor-interacting protein in aging mouse". Age (Dordr) 30 (4): 237–243. 2008. doi:10.1007/s11357-008-9062-3. PMID 19424847. 
  18. ↑ "RIP140 gene and protein expression levels are downregulated in visceral adipose tissue in human morbid obesity". Obes Surg 19 (6): 771–776. 2009. doi:10.1007/s11695-009-9834-6. PMID 19367438. 
  19. ↑ "The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes". Clin Cancer Res 16 (11): 2959–2970. 2010. doi:10.1158/1078-0432.CCR-09-3153. PMID 20410059. 
  20. ↑ "Coactivator function of RIP140 for NFkappaB/RelA-dependent cytokine gene expression". Blood 112 (2): 264–276. 2008. doi:10.1182/blood-2007-11-121699. PMID 18469200. 
  21. ↑ "Differential recruitment of coactivator RIP140 by Ah and estrogen receptors. Absence of a role for LXXLL motifs". J. Biol. Chem. 274 (32): 22155–64. Aug 1999. doi:10.1074/jbc.274.32.22155. PMID 10428779. 
  22. ↑ 22.0 22.1 22.2 Castet A; Boulahtouf Abdelhay; Versini Gwennaëlle; Bonnet Sandrine; Augereau Patrick; Vignon Françoise; Khochbin Saadi; Jalaguier Stéphan et al. (2004). "Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition". Nucleic Acids Res. 32 (6): 1957–66. doi:10.1093/nar/gkh524. PMID 15060175. 
  23. ↑ Perissi V; Scafoglio Claudio; Zhang Jie; Ohgi Kenneth A; Rose David W; Glass Christopher K; Rosenfeld Michael G (Mar 2008). "TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints". Mol. Cell 29 (6): 755–66. doi:10.1016/j.molcel.2008.01.020. PMID 18374649. 
  24. ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R. 
  25. ↑ 25.0 25.1 "RIP 140 modulates transcription of the steroidogenic acute regulatory protein gene through interactions with both SF-1 and DAX-1". Endocrinology 142 (8): 3570–7. August 2001. doi:10.1210/endo.142.8.8309. PMID 11459805. 
  26. ↑ Hu X; Chen Yixin; Farooqui Mariya; Thomas Mary C; Chiang Cheng-Ming; Wei Li-Na (Jan 2004). "Suppressive effect of receptor-interacting protein 140 on coregulator binding to retinoic acid receptor complexes, histone-modifying enzyme activity, and gene activation". J. Biol. Chem. 279 (1): 319–25. doi:10.1074/jbc.M307621200. PMID 14581481. 
  27. ↑ 27.0 27.1 Farooqui M; Franco Peter J; Thompson Jim; Kagechika Hiroyuki; Chandraratna Roshantha A S; Banaszak Len; Wei Li-Na (Feb 2003). "Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity". Biochemistry 42 (4): 971–9. doi:10.1021/bi020497k. PMID 12549917. 
  28. ↑ 28.0 28.1 28.2 "RIP-140 interacts with multiple nuclear receptors by means of two distinct sites". Mol. Cell. Biol. 16 (11): 6029–36. Nov 1996. doi:10.1128/MCB.16.11.6029. PMID 8887632. 
  29. ↑ "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". J. Biol. Chem. 272 (18): 12062–8. May 1997. doi:10.1074/jbc.272.18.12062. PMID 9115274. 
  30. ↑ 30.0 30.1 "Regulation of glucocorticoid receptor activity by 14--3-3-dependent intracellular relocalization of the corepressor RIP140". Mol. Endocrinol. 15 (4): 501–11. Apr 2001. doi:10.1210/mend.15.4.0624. PMID 11266503. 
  31. ↑ Tazawa H; Osman Waffa; Shoji Yutaka; Treuter Eckardt; Gustafsson Jan-Ake; Zilliacus Johanna (Jun 2003). "Regulation of subnuclear localization is associated with a mechanism for nuclear receptor corepression by RIP140". Mol. Cell. Biol. 23 (12): 4187–98. doi:10.1128/MCB.23.12.4187-4198.2003. PMID 12773562. 
  32. ↑ "Receptor interacting protein RIP140 inhibits both positive and negative gene regulation by glucocorticoids". J. Biol. Chem. 274 (25): 18121–7. Jun 1999. doi:10.1074/jbc.274.25.18121. PMID 10364267. 
  33. ↑ Mellgren G; Børud Bente; Hoang Tuyen; Yri Olav Erich; Fladeby Cathrine; Lien Ernst Asbjørn; Lund Johan (May 2003). "Characterization of receptor-interacting protein RIP140 in the regulation of SF-1 responsive target genes". Mol. Cell. Endocrinol. 203 (1–2): 91–103. doi:10.1016/S0303-7207(03)00097-2. PMID 12782406. 

Further reading

External links

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



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