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]
Contents
Function
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
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
Retinoic acid receptor alpha has been shown to interact with:
See also
References
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- ^ 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.
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Further reading
- Petkovich M, Brand NJ, Krust A, Chambon P (1988). "A human retinoic acid receptor which belongs to the family of nuclear receptors". Nature 330 (6147): 444–50. doi:10.1038/330444a0. PMID 2825025.
- Sirulnik A, Melnick A, Zelent A, Licht JD (2003). "Molecular pathogenesis of acute promyelocytic leukaemia and APL variants". Best Pract Res Clin Haematol 16 (3): 387–408. doi:10.1016/S1521-6926(03)00062-8. PMID 12935958.
- Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM (1992). "Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling". Nature 355 (6359): 446–9. doi:10.1038/355446a0. PMID 1310351.
- Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub MP, Durand B et al. (1992). "Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins". EMBO J. 11 (2): 629–42. PMC 556495. PMID 1311253.
- Baniahmad A, Köhne AC, Renkawitz R (1992). "A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor". EMBO J. 11 (3): 1015–23. PMC 556542. PMID 1347744.
- de Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A (1991). "The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR". Cell 66 (4): 675–84. doi:10.1016/0092-8674(91)90113-D. PMID 1652369.
- de Thé H, Chomienne C, Lanotte M, Degos L, Dejean A (1990). "The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus". Nature 347 (6293): 558–61. doi:10.1038/347558a0. PMID 2170850.
- Brand NJ, Petkovich M, Chambon P (1990). "Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha)". Nucleic Acids Res. 18 (23): 6799–806. doi:10.1093/nar/18.23.6799. PMC 332734. PMID 2175878.
- Borrow J, Goddard AD, Sheer D, Solomon E (1990). "Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17". Science 249 (4976): 1577–80. doi:10.1126/science.2218500. PMID 2218500.
- Arveiler B, Petkovich M, Mandel JL, Chambon P (1988). "A PstI RFLP for the human retinoic acid receptor in 17q21". Nucleic Acids Res. 16 (13): 6252. doi:10.1093/nar/16.13.6252. PMC 336887. PMID 2899875.
- Chen JD, Evans RM (1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature 377 (6548): 454–7. doi:10.1038/377454a0. PMID 7566127.
- Fisher GJ, Talwar HS, Xiao JH, Datta SC, Reddy AP, Gaub MP et al. (1994). "Immunological identification and functional quantitation of retinoic acid and retinoid X receptor proteins in human skin". J. Biol. Chem. 269 (32): 20629–35. PMID 8051161.
- Chen Z, Guidez F, Rousselot P, Agadir A, Chen SJ, Wang ZY et al. (1994). "PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors". Proc. Natl. Acad. Sci. U.S.A. 91 (3): 1178–82. doi:10.1073/pnas.91.3.1178. PMC 521477. PMID 8302850.
- Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ (1996). "The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion". Blood 87 (3): 882–6. PMID 8562957.
- Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B et al. (1996). "A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors". Cell 85 (3): 403–14. doi:10.1016/S0092-8674(00)81118-6. PMID 8616895.
- Liu W, Hellman P, Li Q, Yu WR, Juhlin C, Nordlinder H et al. (1996). "Biosynthesis and function of all-trans- and 9-cis-retinoic acid in parathyroid cells". Biochem. Biophys. Res. Commun. 229 (3): 922–9. doi:10.1006/bbrc.1996.1903. PMID 9005841.
- Thénot S, Henriquet C, Rochefort H, Cavaillès V (1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". J. Biol. Chem. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.