NRIP1

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.[5][6]

NRIP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNRIP1, RIP140, nuclear receptor interacting protein 1, CAKUT3
External IDsOMIM: 602490 MGI: 1315213 HomoloGene: 2606 GeneCards: NRIP1
Gene location (Human)
Chr.Chromosome 21 (human)[1]
Band21q11.2-q21.1Start14,961,235 bp[1]
End15,065,936 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

8204

268903

Ensembl

ENSG00000180530

ENSMUSG00000048490

UniProt

P48552

Q8CBD1

RefSeq (mRNA)

NM_003489

NM_173440
NM_001358238

RefSeq (protein)

NP_003480

NP_775616
NP_001345167

Location (UCSC)Chr 21: 14.96 – 15.07 MbChr 16: 76.29 – 76.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
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

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.[7]

RIP140 has an important role in regulating lipid and glucose metabolism,[8] and regulates gene expression in metabolic tissues including heart,[9] skeletal muscle,[10] and liver.[11] 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.[12]

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.[13]

RIP140 suppresses the expression of mitochondrial proteins succinate dehydrogenase complex b and CoxVb and acts as a negative regulator of glucose uptake in mice.[14]

Knockout studies

Knockout mice that completely lack the RIP140 molecule are lean and stay lean, even on a rich diet.[15]

Knockout mice (females) are also infertile because they fail to ovulate.[16] Failure of ovulation in these mice is caused by lack of cumulus expansion and altered expression of various genes, including amphiregulin, in ovarian follicles.[17][18]

Clinical significance

RIP140 is part of the chain by which tumors can cause cachexia.[19][20]

Levels of RIP140 expression in various tissues varies during aging in mice, suggesting changes in metabolic function.[21] RIP140 is implicated in certain human disease processes. In morbid obesity, RIP140 levels are down-regulated in visceral adipose tissue.[22] 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.[23] 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.[24]

Interactions

NRIP1 has been shown to interact with:

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000180530 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000048490 - 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. Cavailles V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG (Sep 1995). "Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor". EMBO J. 14 (15): 3741–51. doi:10.1002/j.1460-2075.1995.tb00044.x. PMC 394449. PMID 7641693.
  6. Katsanis N, Ives JH, Groet J, Nizetic D, Fisher EM (Apr 1998). "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. doi:10.1007/s004390050682. PMID 9521594. S2CID 1042332.
  7. "Entrez Gene: NRIP1 nuclear receptor interacting protein 1".
  8. Rosell M, Jones MC, Parker MG (2010). "Role of nuclear receptor corepressor RIP140 in metabolic syndrome". Biochim Biophys Acta. 1812 (8): 919–28. doi:10.1016/j.bbadis.2010.12.016. PMC 3117993. PMID 21193034.
  9. Fritah A, Steel JH, Nichol D, Parker N, Williams S, Price A, Strauss L, Ryder TA, Mobberley MA, Poutanen M, Parker M, White R (2010). "Elevated expression of the metabolic regulator receptor-interacting protein 140 results in cardiac hypertrophy and impaired cardiac function". Cardiovasc Res. 86 (3): 443–451. doi:10.1093/cvr/cvp418. PMC 2868176. PMID 20083575.
  10. Seth A, Steel JH, Nichol D, Pocock V, Kumaran MK, Fritah A, Mobberley M, Ryder TA, Rowlerson A, Scott J, Poutanen M, White R, Parker M (Sep 2007). "The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle". Cell Metab. 6 (3): 236–245. doi:10.1016/j.cmet.2007.08.004. PMC 2680991. PMID 17767910.
  11. Herzog B, Hallberg M, Seth A, Woods A, White R, Parker MG (Nov 2007). "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. doi:10.1210/ME.2007-0213. PMC 2140279. PMID 17684114.
  12. Debevec D, Christian M, Morganstein D, Seth A, Herzog B, Parker M, White R (July 2007). "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. doi:10.1210/me.2007-0103. PMC 2072047. PMID 17456798.
  13. Nichol D, Christian M, Steel JH, White R, Parker MG (Oct 2006). "RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis". J Biol Chem. 281 (43): 32140–32147. doi:10.1074/jbc.M604803200. PMID 16923809.
  14. Powelka AM, Seth A, Virbasius JV, Kiskinis E, Nicoloro SM, Guilherme A, Tang X, Straubhaar J, Cherniack AD, Parker MG, Czech MP (2006). "Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes". J Clin Invest. 116 (1): 125–136. doi:10.1172/JCI26040. PMC 1319222. PMID 16374519.
  15. Leonardsson G, Steel JH, Christian M, Pocock V, Milligan S, Bell J, So PW, Medina-Gomez G, Vidal-Puig A, White R, Parker MG (May 2004). "Nuclear receptor corepressor RIP140 regulates fat accumulation". Proc Natl Acad Sci U S A. 101 (22): 8437–42. Bibcode:2004PNAS..101.8437L. doi:10.1073/pnas.0401013101. PMC 420412. PMID 15155905.
  16. White R, Leonardsson G, Rosewell I, Ann Jacobs M, Milligan S, Parker M (Dec 2000). "The nuclear receptor co-repressor nrip1 (RIP140) is essential for female fertility". Nat. Med. 6 (12): 1368–74. doi:10.1038/82183. PMID 11100122. S2CID 20285964.
  17. Tullet JM, Pocock V, Steel JH, White R, Milligan S, Parker MG (2005). "Multiple Signaling Defects in the Absence of RIP140 Impair Both Cumulus Expansion and Follicle Rupture". Endocrinology. 146 (9): 4127–4137. doi:10.1210/EN.2005-0348. PMID 15919748.
  18. Nautiyal J, Steel JH, Rosell MM, Nikolopoulou E, Lee K, Demayo FJ, White R, Richards JS, Parker MG (2010). "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. doi:10.1210/EN.2010-0081. PMC 2875814. PMID 20308529.
  19. "A common denominator of inflammations and fatty liver". News. Science Centric. 2008-05-31. Retrieved 2008-08-31.
  20. Diaz MB, Krones-Herzig A, Metzger D, Ziegler A, Vegiopoulos A, Klingenspor M, Müller-Decker K, Herzig S (April 2008). "Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice". Hepatology. 48 (3): 782–791. doi:10.1002/hep.22383. PMID 18712775. S2CID 26235707.
  21. Ghosh S, Thakur MK (2008). "Tissue-specific expression of receptor-interacting protein in aging mouse". Age (Dordr). 30 (4): 237–243. doi:10.1007/s11357-008-9062-3. PMC 2585652. PMID 19424847.
  22. Catalán V, Gómez-Ambrosi J, Lizanzu A, Rodríguez A, Silva C, Rotellar F, Gil MJ, Cienfuegos JA, Salvador J, Frühbeck G (2009). "RIP140 gene and protein expression levels are downregulated in visceral adipose tissue in human morbid obesity". Obes Surg. 19 (6): 771–776. doi:10.1007/s11695-009-9834-6. PMID 19367438. S2CID 787869.
  23. Docquier A, Harmand PO, Fritsch S, Chanrion M, Darbon JM, Cavaillès V (2010). "The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes". Clin Cancer Res. 16 (11): 2959–2970. doi:10.1158/1078-0432.CCR-09-3153. PMC 3112174. PMID 20410059.
  24. Zschiedrich I, Hardeland U, Krones-Herzig A, Berriel DM, Vegiopoulos A, Müggenburg J, Sombroek D, Hofmann TG, Zawatzky R, Yu X, Gretz N, Christian M, White R, Parker MG, Herzig S (2008). "Coactivator function of RIP140 for NFkappaB/RelA-dependent cytokine gene expression". Blood. 112 (2): 264–276. doi:10.1182/blood-2007-11-121699. PMID 18469200.
  25. Kumar MB, Tarpey RW, Perdew GH (Aug 1999). "Differential recruitment of coactivator RIP140 by Ah and estrogen receptors. Absence of a role for LXXLL motifs". J. Biol. Chem. 274 (32): 22155–64. doi:10.1074/jbc.274.32.22155. PMID 10428779.
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Further reading


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