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Gene Review

Rara  -  retinoic acid receptor, alpha

Mus musculus

Synonyms: Nr1b1, Nuclear receptor subfamily 1 group B member 1, RAR, RAR alpha 1, RAR-alpha, ...
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Disease relevance of Rara


Psychiatry related information on Rara


High impact information on Rara

  • The fusion protein PML-RARalpha, generated by the t(15;17)(q22;q11.2) translocation associated with acute promyelocytic leukemia (APL), initiates APL when expressed in the early myeloid compartment of transgenic mice [7].
  • Since NE is maximally produced in promyelocytes, this protease may play a role in APL pathogenesis by facilitating the leukemogenic potential of PML-RARalpha [7].
  • Here we show that ureter maturation depends on formation of the 'trigonal wedge', a newly identified epithelial outgrowth from the base of the Wolffian ducts, and that the distal ureter abnormalities seen in Rara(-/-) Rarb2(-/-) and Ret(-/-) mutant mice are probably caused by a failure of this process [8].
  • We report a hormone-dependent interaction of the nuclear receptors, RAR alpha and RXR alpha, with CLOCK and MOP4 [9].
  • Recombinant RAR alpha was phosphorylated by a variety of proline-directed protein kinases in vitro [10].

Chemical compound and disease context of Rara


Biological context of Rara


Anatomical context of Rara

  • Here we demonstrate that forced expression of Ret in mice deficient for both Rara and Rarb2 (Rara(-/-)Rarb2(-/-)) genetically rescues renal development, restoring ureteric bud growth and stromal cell patterning [17].
  • All RAR-mediated signalling pathways are therefore dispensable in epidermis for homeostatic keratinocyte renewal [1].
  • These results demonstrate a specific function for RARalpha in limb development and the regulation of chondroblast differentiation [20].
  • To address the biological function of the alpha 1 receptor, we have disrupted the portion of the RAR alpha gene encoding this isoform by homologous recombination in mouse embryonic stem cells [21].
  • Within their expression domains in the spinal cord and brain, RAR-alpha was ubiquitously expressed, whereas RAR-beta transcripts showed very specific patterns of expression, suggesting that this receptor is involved in mediating retinoic acid-induced gene expression in relation to the development of specific neural structures or pathways [22].

Associations of Rara with chemical compounds


Physical interactions of Rara


Regulatory relationships of Rara

  • RAR alpha- and gamma-selective retinoids induced Bmp-2 and repressed Bmp-4 equally as well as all-trans RA [33].
  • In response to RA, RARbeta2 transcription is epigenetically regulated by RARalpha [34].
  • In contrast, transcripts encoding Hoxb-1 (Hox-2.9) and cellular RA binding protein II (CRABPII) are activated by RA for a longer period of time in the RAR gamma-/- lines compared to the wild-type F9 line [35].
  • BMP-7 was globally down-regulated at an early stage in the autopods of these RAR double null mutants, prior to the appearance of the digital rays [36].
  • PML-RARalpha has been shown to promote transcriptional repression of genes involved in myeloid terminal differentiation and to disrupt the architecture of PML bodies, a phenotype reversed by treatment with all trans retinoic acid (ATRA) [37].

Other interactions of Rara


Analytical, diagnostic and therapeutic context of Rara

  • Thus, the dissection of this transcription system ultimately should lead to the elucidation of the molecular mechanisms by which RAR/RXR heterodimers control transcription in a ligand-dependent manner [38].
  • In the present study, the expression of retinoic acid receptors (RAR alpha, beta and gamma) and retinoid X receptors (RXR alpha, beta and gamma) was examined by Northern blot analysis in rat adipose tissue and mouse 3T3-L1 adipose cells [40].
  • In a more detailed time course, application of 20 nmol of TPA to mouse skin led to 20, 36, 92 and 0% decrease in the binding of [3H]RA to mouse epidermal RAR at 2, 4, 12 and 72 h after treatment respectively [41].
  • This study used in situ hybridization to describe the expression patterns of RARalpha1, RARalpha2, RARbeta1/3, RARbeta2/4, RARgamma1 and RARgamma2 isoform transcripts during mouse embryogenesis [42].
  • Electrophoretic mobility shift assays with nuclear extracts show specific binding to the beta RARE (Complex I) in untreated cells, which can be supershifted by antibodies against RXRs but not by anti-RAR antibodies [43].


  1. Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled. Chapellier, B., Mark, M., Messaddeq, N., Calléja, C., Warot, X., Brocard, J., Gérard, C., Li, M., Metzger, D., Ghyselinck, N.B., Chambon, P. EMBO J. (2002) [Pubmed]
  2. Reexpression of retinoic acid receptor (RAR) gamma or overexpression of RAR alpha or RAR beta in RAR gamma-null F9 cells reveals a partial functional redundancy between the three RAR types. Taneja, R., Bouillet, P., Boylan, J.F., Gaub, M.P., Roy, B., Gudas, L.J., Chambon, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Overexpression of wild-type retinoic acid receptor alpha (RARalpha) recapitulates retinoic acid-sensitive transformation of primary myeloid progenitors by acute promyelocytic leukemia RARalpha-fusion genes. Du, C., Redner, R.L., Cooke, M.P., Lavau, C. Blood (1999) [Pubmed]
  4. Regulation of retinoic acid receptor alpha by protein kinase C in B16 mouse melanoma cells. Boskovic, G., Desai, D., Niles, R.M. J. Biol. Chem. (2002) [Pubmed]
  5. Overexpression of dominant negative retinoic acid receptor alpha causes alveolar abnormality in transgenic neonatal lungs. Yang, L., Naltner, A., Yan, C. Endocrinology (2003) [Pubmed]
  6. The nuclear transcription factor RARalpha associates with neuronal RNA granules and suppresses translation. Chen, N., Onisko, B., Napoli, J.L. J. Biol. Chem. (2008) [Pubmed]
  7. Neutrophil elastase cleaves PML-RARalpha and is important for the development of acute promyelocytic leukemia in mice. Lane, A.A., Ley, T.J. Cell (2003) [Pubmed]
  8. Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Batourina, E., Choi, C., Paragas, N., Bello, N., Hensle, T., Costantini, F.D., Schuchardt, A., Bacallao, R.L., Mendelsohn, C.L. Nat. Genet. (2002) [Pubmed]
  9. Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. McNamara, P., Seo, S.P., Rudic, R.D., Sehgal, A., Chakravarti, D., FitzGerald, G.A. Cell (2001) [Pubmed]
  10. Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Rochette-Egly, C., Adam, S., Rossignol, M., Egly, J.M., Chambon, P. Cell (1997) [Pubmed]
  11. Cyclic AMP analogs and retinoic acid influence the expression of retinoic acid receptor alpha, beta, and gamma mRNAs in F9 teratocarcinoma cells. Hu, L., Gudas, L.J. Mol. Cell. Biol. (1990) [Pubmed]
  12. Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin-resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding topoisomerase IIalpha and the retinoic acid receptor alpha locus. McPherson, J.P., Brown, G.A., Goldenberg, G.J. Cancer Res. (1993) [Pubmed]
  13. Peroxisome proliferators disrupt retinoic acid receptor alpha signaling in the testis. Dufour, J.M., Vo, M.N., Bhattacharya, N., Okita, J., Okita, R., Kim, K.H. Biol. Reprod. (2003) [Pubmed]
  14. Efficacy of all-trans-beta-carotene, canthaxanthin, and all-trans-, 9-cis-, and 4-oxoretinoic acids in inducing differentiation of an F9 embryonal carcinoma RAR beta-lacZ reporter cell line. Nikawa, T., Schulz, W.A., van den Brink, C.E., Hanusch, M., van der Saag, P., Stahl, W., Sies, H. Arch. Biochem. Biophys. (1995) [Pubmed]
  15. Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML-RARalpha independent manner. Wang, Z.G., Rivi, R., Delva, L., König, A., Scheinberg, D.A., Gambacorti-Passerini, C., Gabrilove, J.L., Warrell, R.P., Pandolfi, P.P. Blood (1998) [Pubmed]
  16. Genetic mapping of a pulmonary adenoma resistance (Par1) in mouse. Manenti, G., Gariboldi, M., Elango, R., Fiorino, A., De Gregorio, L., Falvella, F.S., Hunter, K., Housman, D., Pierotti, M.A., Dragani, T.A. Nat. Genet. (1996) [Pubmed]
  17. Vitamin A controls epithelial/mesenchymal interactions through Ret expression. Batourina, E., Gim, S., Bello, N., Shy, M., Clagett-Dame, M., Srinivas, S., Costantini, F., Mendelsohn, C. Nat. Genet. (2001) [Pubmed]
  18. Analysis of the retinoic acid receptor alpha gene as a candidate for the pulmonary adenoma resistance 1 gene. Gariboldi, M., Vivat, V., De Gregorio, L., Manenti, G., Chiariello, E., Falvella, F.S., Pierotti, M.A., Dragani, T.A. Mol. Carcinog. (1998) [Pubmed]
  19. Allelic fusion of DNA topoisomerase II alpha and retinoic acid receptor alpha genes in adriamycin-resistant p388 murine leukemia revealed by fluorescence in situ hybridization. Squire, J.A., McPherson, J.P., Beatty, B.G., Goldenberg, G.J. Cytogenet. Cell Genet. (1996) [Pubmed]
  20. Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis. Cash, D.E., Bock, C.B., Schughart, K., Linney, E., Underhill, T.M. J. Cell Biol. (1997) [Pubmed]
  21. Normal development and growth of mice carrying a targeted disruption of the alpha 1 retinoic acid receptor gene. Li, E., Sucov, H.M., Lee, K.F., Evans, R.M., Jaenisch, R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  22. Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Ruberte, E., Friederich, V., Chambon, P., Morriss-Kay, G. Development (1993) [Pubmed]
  23. A new mutation Rim3 resembling Re(den) is mapped close to retinoic acid receptor alpha (Rara) gene on mouse chromosome 11. Sato, H., Koide, T., Masuya, H., Wakana, S., Sagai, T., Umezawa, A., Ishiguro, S., Tamai, M., Shiroishi, T., Tama, M. Mamm. Genome (1998) [Pubmed]
  24. Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. Lallemand-Breitenbach, V., Zhu, J., Puvion, F., Koken, M., Honoré, N., Doubeikovsky, A., Duprez, E., Pandolfi, P.P., Puvion, E., Freemont, P., de Thé, H. J. Exp. Med. (2001) [Pubmed]
  25. Roles of retinoic acid receptors in early embryonic morphogenesis and hindbrain patterning. Wendling, O., Ghyselinck, N.B., Chambon, P., Mark, M. Development (2001) [Pubmed]
  26. Specificity of retinoid receptor gene expression in mouse cervical epithelia. Darwiche, N., Celli, G., De Luca, L.M. Endocrinology (1994) [Pubmed]
  27. Lysine trimethylation of retinoic acid receptor-alpha: a novel means to regulate receptor function. Huq, M.D., Tsai, N.P., Khan, S.A., Wei, L.N. Mol. Cell Proteomics (2007) [Pubmed]
  28. The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements. Desai-Yajnik, V., Samuels, H.H. Mol. Cell. Biol. (1993) [Pubmed]
  29. Negative regulation of a special, double AP-1 consensus element in the vimentin promoter: interference by the retinoic acid receptor. Van de Klundert, F.A., Jansen, H.J., Bloemendal, H. J. Cell. Physiol. (1995) [Pubmed]
  30. Modulation of the retinoic acid and retinoid X receptor signaling pathways in P19 embryonal carcinoma cells by calreticulin. Shago, M., Flock, G., Leung Hagesteijn, C.Y., Woodside, M., Grinstein, S., Giguère, V., Dedhar, S. Exp. Cell Res. (1997) [Pubmed]
  31. Close linkage of retinoic acid receptor genes with homeobox- and keratin-encoding genes on paralogous segments of mouse chromosomes 11 and 15. Nadeau, J.H., Compton, J.G., Giguère, V., Rossant, J., Varmuza, S. Mamm. Genome (1992) [Pubmed]
  32. Distinct binding determinants for 9-cis retinoic acid are located within AF-2 of retinoic acid receptor alpha. Tate, B.F., Allenby, G., Janocha, R., Kazmer, S., Speck, J., Sturzenbecker, L.J., Abarzúa, P., Levin, A.A., Grippo, J.F. Mol. Cell. Biol. (1994) [Pubmed]
  33. Receptor-selective retinoids implicate retinoic acid receptor alpha and gamma in the regulation of bmp-2 and bmp-4 in F9 embryonal carcinoma cells. Rogers, M.B. Cell Growth Differ. (1996) [Pubmed]
  34. RAR-mediated epigenetic control of the cytochrome P450 Cyp26a1 in embryocarcinoma cells. Pozzi, S., Rossetti, S., Bistulfi, G., Sacchi, N. Oncogene (2006) [Pubmed]
  35. Loss of retinoic acid receptor gamma function in F9 cells by gene disruption results in aberrant Hoxa-1 expression and differentiation upon retinoic acid treatment. Boylan, J.F., Lohnes, D., Taneja, R., Chambon, P., Gudas, L.J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  36. Essential roles of retinoic acid signaling in interdigital apoptosis and control of BMP-7 expression in mouse autopods. Dupé, V., Ghyselinck, N.B., Thomazy, V., Nagy, L., Davies, P.J., Chambon, P., Mark, M. Dev. Biol. (1999) [Pubmed]
  37. Pro-proliferative function of the long isoform of PML-RARalpha involved in acute promyelocytic leukemia. Tussié-Luna, M.I., Rozo, L., Roy, A.L. Oncogene (2006) [Pubmed]
  38. Ligand-dependent activation of transcription in vitro by retinoic acid receptor alpha/retinoid X receptor alpha heterodimers that mimics transactivation by retinoids in vivo. Dilworth, F.J., Fromental-Ramain, C., Remboutsika, E., Benecke, A., Chambon, P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  39. Inhibition of PPAR alpha/RXR alpha-mediated direct hyperplasia pathways during griseofulvin-induced hepatocarcinogenesis. Nagao, Y., French, B.A., Cai, Y., French, S.W., Wan, Y.J. J. Cell. Biochem. (1998) [Pubmed]
  40. Retinoic acid receptor gamma 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes. Kamei, Y., Kawada, T., Kazuki, R., Sugimoto, E. Biochem. J. (1993) [Pubmed]
  41. Retinoic acid nuclear receptors and tumor promotion: decreased expression of retinoic acid nuclear receptors by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Kumar, R., Shoemaker, A.R., Verma, A.K. Carcinogenesis (1994) [Pubmed]
  42. Tissue-specific expression of retinoic acid receptor isoform transcripts in the mouse embryo. Mollard, R., Viville, S., Ward, S.J., Décimo, D., Chambon, P., Dollé, P. Mech. Dev. (2000) [Pubmed]
  43. Evidence that retinoid X receptors mediate retinoid-dependent transcriptional activation of the retinoic acid receptor beta gene in S91 melanoma cells. Spanjaard, R.A., Sugawara, A., Ikeda, M., Chin, W.W. J. Biol. Chem. (1995) [Pubmed]
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