Retinoic acid receptor alpha

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Retinoic acid receptor, alpha
Protein RARA PDB 1dkf.png
PDB rendering based on 1dkf.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RARA ; NR1B1; RAR
External IDs OMIM180240 MGI97856 HomoloGene20262 IUPHAR: 590 ChEMBL: 2055 GeneCards: RARA Gene
RNA expression pattern
PBB GE RARA 203749 s at tn.png
PBB GE RARA 203750 s at tn.png
PBB GE RARA 211605 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5914 19401
Ensembl ENSG00000131759 ENSMUSG00000037992
UniProt P10276 P11416
RefSeq (mRNA) NM_000964 NM_001176528
RefSeq (protein) NP_000955 NP_001169999
Location (UCSC) Chr 17:
40.31 – 40.36 Mb
Chr 11:
98.93 – 98.97 Mb
PubMed search [1] [2]

Retinoic acid receptor alpha (RAR-α), also known as NR1B1 (nuclear receptor subfamily 1, group B, member 1) is a nuclear receptor that in humans is encoded by the RARA gene.[1][2]

Function[edit]

Retinoid signaling is transduced by 2 families of nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), which form RXR/RAR heterodimers. In the absence of ligand, DNA-bound RXR/RARA represses transcription by recruiting the corepressors NCOR1, SMRT (NCOR2), and histone deacetylase. When ligand binds to the complex, it induces a conformational change allowing the recruitment of coactivators, histone acetyltransferases, and the basic transcription machinery.[3]

Clinical significance[edit]

Translocations that always involve rearrangement of the RARA gene are a cardinal feature of acute promyelocytic leukemia (APL; MIM 612376). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the PML gene.[4]

Interactions[edit]

Retinoic acid receptor alpha has been shown to interact with:

See also[edit]

References[edit]

  1. ^ Giguere V, Ong ES, Segui P, Evans RM (1987). "Identification of a receptor for the morphogen retinoic acid". Nature 330 (6149): 624–9. doi:10.1038/330624a0. PMID 2825036. 
  2. ^ Anderson LA, Friedman L, Osborne-Lawrence S, Lynch E, Weissenbach J, Bowcock A et al. (September 1993). "High-density genetic map of the BRCA1 region of chromosome 17q12-q21". Genomics 17 (3): 618–23. doi:10.1006/geno.1993.1381. PMID 8244378. 
  3. ^ "Entrez Gene: retinoic acid receptor". 
  4. ^ Vitoux D, Nasr R, de The H (2007). "Acute promyelocytic leukemia: new issues on pathogenesis and treatment response". Int. J. Biochem. Cell Biol. 39 (6): 1063–70. doi:10.1016/j.biocel.2007.01.028. PMID 17468032. 
  5. ^ Liu R, Takayama S, Zheng Y, Froesch B, Chen GQ, Zhang X et al. (July 1998). "Interaction of BAG-1 with retinoic acid receptor and its inhibition of retinoic acid-induced apoptosis in cancer cells". J. Biol. Chem. 273 (27): 16985–92. doi:10.1074/jbc.273.27.16985. PMID 9642262. 
  6. ^ a b McNamara P, Seo SB, Rudic RD, Sehgal A, Chakravarti D, FitzGerald GA (June 2001). "Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock". Cell 105 (7): 877–89. doi:10.1016/S0092-8674(01)00401-9. PMID 11439184. 
  7. ^ Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C et al. (February 2003). "Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II". J. Biol. Chem. 278 (8): 6355–62. doi:10.1074/jbc.M210697200. PMID 12482873. 
  8. ^ Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (February 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Mol. Endocrinol. 15 (2): 241–54. doi:10.1210/me.15.2.241. PMID 11158331. 
  9. ^ Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK et al. (November 1999). "A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo". J. Biol. Chem. 274 (48): 34283–93. doi:10.1074/jbc.274.48.34283. PMID 10567404. 
  10. ^ Ko L, Cardona GR, Chin WW (May 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6212–7. doi:10.1073/pnas.97.11.6212. PMC 18584. PMID 10823961. 
  11. ^ Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (May 1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". J. Biol. Chem. 274 (22): 15901–7. doi:10.1074/jbc.274.22.15901. PMID 10336495. 
  12. ^ Guidez F, Ivins S, Zhu J, Söderström M, Waxman S, Zelent A (April 1998). "Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia". Blood 91 (8): 2634–42. PMID 9531570. 
  13. ^ Dong S, Tweardy DJ (April 2002). "Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways". Blood 99 (8): 2637–46. doi:10.1182/blood.V99.8.2637. PMID 11929748. 
  14. ^ Hong SH, David G, Wong CW, Dejean A, Privalsky ML (August 1997). "SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor alpha (RARalpha) and PLZF-RARalpha oncoproteins associated with acute promyelocytic leukemia". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9028–33. doi:10.1073/pnas.94.17.9028. PMC 23013. PMID 9256429. 
  15. ^ Hu X, Chen Y, Farooqui M, Thomas MC, Chiang CM, Wei LN (January 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. 
  16. ^ Farooqui M, Franco PJ, Thompson J, Kagechika H, Chandraratna RA, Banaszak L et al. (February 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. 
  17. ^ L'Horset F, Dauvois S, Heery DM, Cavaillès V, Parker MG (November 1996). "RIP-140 interacts with multiple nuclear receptors by means of two distinct sites". Mol. Cell. Biol. 16 (11): 6029–36. PMC 231605. PMID 8887632. 
  18. ^ Seol W, Choi HS, Moore DD (May 1996). "An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors". Science 272 (5266): 1336–9. doi:10.1126/science.272.5266.1336. PMID 8650544. 
  19. ^ Seol W, Hanstein B, Brown M, Moore DD (October 1998). "Inhibition of estrogen receptor action by the orphan receptor SHP (short heterodimer partner)". Mol. Endocrinol. 12 (10): 1551–7. doi:10.1210/me.12.10.1551. PMID 9773978. 
  20. ^ Perlmann T, Jansson L (April 1995). "A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1". Genes Dev. 9 (7): 769–82. doi:10.1101/gad.9.7.769. PMID 7705655. 
  21. ^ Zhong S, Delva L, Rachez C, Cenciarelli C, Gandini D, Zhang H et al. (November 1999). "A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins". Nat. Genet. 23 (3): 287–95. doi:10.1038/15463. PMID 10610177. 
  22. ^ Benkoussa M, Brand C, Delmotte MH, Formstecher P, Lefebvre P (July 2002). "Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter". Mol. Cell. Biol. 22 (13): 4522–34. doi:10.1128/MCB.22.13.4522-4534.2002. PMC 133906. PMID 12052862. 
  23. ^ Bugge TH, Pohl J, Lonnoy O, Stunnenberg HG (April 1992). "RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors". EMBO J. 11 (4): 1409–18. PMC 556590. PMID 1314167. 
  24. ^ Kim HJ, Yi JY, Sung HS, Moore DD, Jhun BH, Lee YC et al. (September 1999). "Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation". Mol. Cell. Biol. 19 (9): 6323–32. PMC 84603. PMID 10454579. 
  25. ^ He B, Wilson EM (March 2003). "Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs". Mol. Cell. Biol. 23 (6): 2135–50. doi:10.1128/MCB.23.6.2135-2150.2003. PMC 149467. PMID 12612084. 
  26. ^ Zeng M, Kumar A, Meng G, Gao Q, Dimri G, Wazer D et al. (November 2002). "Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator". J. Biol. Chem. 277 (47): 45611–8. doi:10.1074/jbc.M208447200. PMID 12235159. 
  27. ^ Martin PJ, Delmotte MH, Formstecher P, Lefebvre P (September 2003). "PLZF is a negative regulator of retinoic acid receptor transcriptional activity". Nucl. Recept. 1 (1): 6. doi:10.1186/1478-1336-1-6. PMC 212040. PMID 14521715. 

Further reading[edit]

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