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Target not currently curated in GtoImmuPdb
Target id: 590
Nomenclature: Retinoic acid receptor-α
Systematic Nomenclature: NR1B1
Family: 1B. Retinoic acid receptors
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 462 | 17q21.2 | RARA | retinoic acid receptor alpha | 49,55 |
| Mouse | 462 | 11 62.76 cM | Rara | retinoic acid receptor, alpha | 40-41,49,73 |
| Rat | 459 | 10 | Rara | retinoic acid receptor, alpha | 1,49 |
| Previous and Unofficial Names |
| RAR alpha 1 | RAR | RARα | retinoic acid receptor |
| Database Links |
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| Alphafold | P10276 (Hs), P11416 (Mm) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL2055 (Hs), CHEMBL2792 (Mm) |
| DrugBank Target | P10276 (Hs) |
| Ensembl Gene | ENSG00000131759 (Hs), ENSMUSG00000037992 (Mm), ENSRNOG00000009972 (Rn) |
| Entrez Gene | 5914 (Hs), 19401 (Mm), 24705 (Rn) |
| Human Protein Atlas | ENSG00000131759 (Hs) |
| KEGG Gene | hsa:5914 (Hs), mmu:19401 (Mm), rno:24705 (Rn) |
| OMIM | 180240 (Hs) |
| Orphanet | ORPHA118227 (Hs) |
| Pharos | P10276 (Hs) |
| RefSeq Nucleotide | NM_001145302 (Hs), NM_001177302 (Mm), NM_009024 (Mm), NM_001177303 (Mm), NM_001176528 (Mm), NM_031528 (Rn) |
| RefSeq Protein | NP_001138773 (Hs), NP_001019980 (Hs), NP_033050 (Mm), NP_113716 (Rn) |
| SynPHARM |
6273 (in complex with BMS614) 83084 (in complex with Ro 40-6055) 7547 (in complex with Ro 40-6055) 79003 (in complex with tretinoin) |
| UniProtKB | P10276 (Hs), P11416 (Mm) |
| Wikipedia | RARA (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| tretinoin |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| All-trans-retinoic acid is the most potent endogenous retinoid. The existence of 9-cis retinoic acid as a natural bioactive retinoid remains to be established. Synthetic compounds (reported above) are not metabolized by CYP26. No significant species variation has been reported. The possibility of establishing a hydrogen bond between an amino group present in the linker of the identified RARα-selective agonists and the RARα-specific Ser232 is predicted to favour RARα selectivity. Adapalene is selective for the β and γ RARs over the α isoform [10]. |
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| Antagonists |
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| No significant species variation has been reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immuno Process Associations | ||||||||||||
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| DNA Binding |
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| DNA Binding Comments | |||||||
| The classical sequence is a 5-pb-spaced direct repeat (DR5). In DR5 and DR2 RXR occupies the 5' element, whereas RARa occupies the 3' one (5'-RXR-RARa-3'). In DR1 elements, the polarity of these elements is inverted (5'-RARa-RXR-3'). | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| cyclin H/cdk7/TFIIH | Physical, Functional | TFIIH phosphorylates RARa1 in its A/B region (ser 77) by cdk7 subunit. | 7,56-57 |
| AP-1 | Physical, Functional | RAR inhibits AP-1 driven transactivation and AP-1 represses RAR-mediated transcription | 13,36,52,62,74 |
| CRABPII | Physical, Functional | Indispensable to RARα-mediated transcription from the RARα2 | 21 |
| PARP-1 | Physical, Functional | Indispensable to RARα-mediated transcription from the RARα2 | 54 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NCOA1 | Co-activator | No | Yes | Yes | A member of the p160 family | 53,71 |
| NCOR1 | Co-repressor | No | No | No | Binding of an agonist to RARa causes NCoR dissociation | 30,50 |
| EP300 | Co-activator | No | Yes | Yes | A common cointegrator | 28 |
| CREBBP | Co-activator | No | Yes | Yes | A common cointegrator | 28 |
| MED1 | Co-activator | No | Yes | Yes | A member of the DRIP/TRAP/SMCC complex | 28,37,47 |
| NCOA3 | Co-activator | No | Yes | Yes | A member of the p160 family | 12 |
| NCOA2 | Co-activator | No | Yes | Yes | A member of the p160 family | 70 |
| NCOR2 | Co-repressor | No | No | No | Binding of an agonist to RARa causes SMRT dissociation | 13,61,72 |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| CYP26 | Human | Activated | Footprint, Transient transfection,ChIP,EMSA | CYP26 is also activated by RARa in mouse and rat. Note: promoter harbors a DR5 element. | 45 |
| RARB | Human | Activated | Footprint, Transient transfection,ChIP,EMSA | Activation is seen across all species including mouse and rat. Note: promoter harbors a DR5 element. | 14,16,18,26 |
| Crabp2 | Mouse | Activated | Transient transfection, EMSA | Promoter harbors a DR2 element. | 16,25 |
| Hoxa1 | Mouse | Activated | Promoter harbors a DR5 element. | 16,24,38 | |
| Rbp1 | Mouse | Activated | Transient transfection | Promoter harbors a DR2 element. | 16,63 |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Ubiquitous distribution pattern of the Rarα1 is also reported in both the mouse and rat. | ||||||||
| Functional Assays
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| Note that both the specific RARα1 null and RARα2 null mutants are apparently normal. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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1. Akmal KM, Dufour JM, Kim KH. (1996) Region-specific localization of retinoic acid receptor-alpha expression in the rat epididymis. Biol Reprod, 54 (5): 1111-9. [PMID:8722633]
2. Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P. (1993) Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA, 90 (1): 30-4. [PMID:8380496]
3. Altucci L, Rossin A, Raffelsberger W, Reitmair A, Chomienne C, Gronemeyer H. (2001) Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Nat Med, 7 (6): 680-6. [PMID:11385504]
4. Apfel C, Bauer F, Crettaz M, Forni L, Kamber M, Kaufmann F, LeMotte P, Pirson W, Klaus M. (1992) A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects. Proc Natl Acad Sci USA, 89 (15): 7129-33. [PMID:1323127]
5. Beard RL, Duong TT, Teng M, Klein ES, Standevan AM, Chandraratna RA. (2002) Synthesis and biological activity of retinoic acid receptor-alpha specific amides. Bioorg Med Chem Lett, 12 (21): 3145-8. [PMID:12372520]
6. Bernard BA, Bernardon JM, Delescluse C, Martin B, Lenoir MC, Maignan J, Charpentier B, Pilgrim WR, Reichert U, Shroot B. (1992) Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun, 186 (2): 977-83. [PMID:1323296]
7. Bour G, Gaillard E, Bruck N, Lalevée S, Plassat JL, Busso D, Samama JP, Rochette-Egly C. (2005) Cyclin H binding to the RARalpha activation function (AF)-2 domain directs phosphorylation of the AF-1 domain by cyclin-dependent kinase 7. Proc Natl Acad Sci USA, 102 (46): 16608-13. [PMID:16275922]
8. Bourguet W, Vivat V, Wurtz JM, Chambon P, Gronemeyer H, Moras D. (2000) Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains. Mol Cell, 5 (2): 289-98. [PMID:10882070]
9. 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. [PMID:2175878]
10. Charpentier B, Bernardon JM, Eustache J, Millois C, Martin B, Michel S, Shroot B. (1995) Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes. J Med Chem, 38 (26): 4993-5006. [PMID:8544175]
11. Charton J, Deprez-Poulain R, Hennuyer N, Tailleux A, Staels B, Deprez B. (2009) Novel non-carboxylic acid retinoids: 1,2,4-oxadiazol-5-one derivatives. Bioorg Med Chem Lett, 19 (2): 489-92. [PMID:19058965]
12. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM. (1997) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell, 90 (3): 569-80. [PMID:9267036]
13. Chen JD, Evans RM. (1995) A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature, 377 (6548): 454-7. [PMID:7566127]
14. Chen JY, Clifford J, Zusi C, Starrett J, Tortolani D, Ostrowski J, Reczek PR, Chambon P, Gronemeyer H. (1996) Two distinct actions of retinoid-receptor ligands. Nature, 382 (6594): 819-22. [PMID:8752277]
15. Chen JY, Penco S, Ostrowski J, Balaguer P, Pons M, Starrett JE, Reczek P, Chambon P, Gronemeyer H. (1995) RAR-specific agonist/antagonists which dissociate transactivation and AP1 transrepression inhibit anchorage-independent cell proliferation. EMBO J, 14 (6): 1187-97. [PMID:7720709]
16. Chiba H, Clifford J, Metzger D, Chambon P. (1997) Distinct retinoid X receptor-retinoic acid receptor heterodimers are differentially involved in the control of expression of retinoid target genes in F9 embryonal carcinoma cells. Mol Cell Biol, 17 (6): 3013-20. [PMID:9154799]
17. Dawson MI, Chao WR, Pine P, Jong L, Hobbs PD, Rudd CK, Quick TC, Niles RM, Zhang XK, Lombardo A. (1995) Correlation of retinoid binding affinity to retinoic acid receptor alpha with retinoid inhibition of growth of estrogen receptor-positive MCF-7 mammary carcinoma cells. Cancer Res, 55 (19): 4446-51. [PMID:7671258]
18. de Thé H, Vivanco-Ruiz MM, Tiollais P, Stunnenberg H, Dejean A. (1990) Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature, 343 (6254): 177-80. [PMID:2153268]
19. Degos L, Wang ZY. (2001) All trans retinoic acid in acute promyelocytic leukemia. Oncogene, 20 (49): 7140-5. [PMID:11704842]
20. Delescluse C, Cavey MT, Martin B, Bernard BA, Reichert U, Maignan J, Darmon M, Shroot B. (1991) Selective high affinity retinoic acid receptor alpha or beta-gamma ligands. Mol Pharmacol, 40 (4): 556-62. [PMID:1656191]
21. Delva L, Bastie JN, Rochette-Egly C, Kraïba R, Balitrand N, Despouy G, Chambon P, Chomienne C. (1999) Physical and functional interactions between cellular retinoic acid binding protein II and the retinoic acid-dependent nuclear complex. Mol Cell Biol, 19 (10): 7158-67. [PMID:10490651]
22. Dollé P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, Chambon P. (1989) Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature, 342 (6250): 702-5. [PMID:2556642]
23. Dollé P, Ruberte E, Leroy P, Morriss-Kay G, Chambon P. (1990) Retinoic acid receptors and cellular retinoid binding proteins. I. A systematic study of their differential pattern of transcription during mouse organogenesis. Development, 110 (4): 1133-51. [PMID:1966045]
24. Dupé V, Davenne M, Brocard J, Dollé P, Mark M, Dierich A, Chambon P, Rijli FM. (1997) In vivo functional analysis of the Hoxa-1 3' retinoic acid response element (3'RARE). Development, 124 (2): 399-410. [PMID:9053316]
25. Durand B, Saunders M, Leroy P, Leid M, Chambon P. (1992) All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs. Cell, 71 (1): 73-85. [PMID:1327537]
26. Germain P, Iyer J, Zechel C, Gronemeyer H. (2002) Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature, 415 (6868): 187-92. [PMID:11805839]
27. Giguere V, Ong ES, Segui P, Evans RM. (1987) Identification of a receptor for the morphogen retinoic acid. Nature, 330 (6149): 624-9. [PMID:2825036]
28. Goodman RH, Smolik S. (2000) CBP/p300 in cell growth, transformation, and development. Genes Dev, 14 (13): 1553-77. [PMID:10887150]
29. Géhin M, Vivat V, Wurtz JM, Losson R, Chambon P, Moras D, Gronemeyer H. (1999) Structural basis for engineering of retinoic acid receptor isotype-selective agonists and antagonists. Chem Biol, 6 (8): 519-29. [PMID:10421757]
30. Hörlein AJ, Näär AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A, Kamei Y, Söderström M, Glass CK. (1995) Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature, 377 (6548): 397-404. [PMID:7566114]
31. Kagechika H, Kawachi E, Hashimoto Y, Himi T, Shudo K. (1988) Retinobenzoic acids. 1. Structure-activity relationships of aromatic amides with retinoidal activity. J Med Chem, 31 (11): 2182-92. [PMID:3184125]
32. Keidel S, LeMotte P, Apfel C. (1994) Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping. Mol Cell Biol, 14 (1): 287-98. [PMID:8264595]
33. Klaholz BP, Mitschler A, Moras D. (2000) Structural basis for isotype selectivity of the human retinoic acid nuclear receptor. J Mol Biol, 302 (1): 155-70. [PMID:10964567]
34. Klein ES, Pino ME, Johnson AT, Davies PJ, Nagpal S, Thacher SM, Krasinski G, Chandraratna RA. (1996) Identification and functional separation of retinoic acid receptor neutral antagonists and inverse agonists. J Biol Chem, 271 (37): 22692-6. [PMID:8798442]
35. Klein ES, Wang JW, Khalifa B, Gavigan SA, Chandraratna RA. (2000) Recruitment of nuclear receptor corepressor and coactivator to the retinoic acid receptor by retinoid ligands. Influence of DNA-heterodimer interactions. J Biol Chem, 275 (25): 19401-8. [PMID:10777502]
36. Lafyatis R, Kim SJ, Angel P, Roberts AB, Sporn MB, Karin M, Wilder RL. (1990) Interleukin-1 stimulates and all-trans-retinoic acid inhibits collagenase gene expression through its 5' activator protein-1-binding site. Mol Endocrinol, 4 (7): 973-80. [PMID:2178224]
37. Lanotte M, Martin-Thouvenin V, Najman S, Balerini P, Valensi F, Berger R. (1991) NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Blood, 77 (5): 1080-6. [PMID:1995093]
38. Laudet V, Gronemeyer H. (2002) The Nuclear Receptor Facts Book. In The Nuclear Receptor Facts Book. (Academic Press) .
39. le Maire A, Teyssier C, Erb C, Grimaldi M, Alvarez S, de Lera AR, Balaguer P, Gronemeyer H, Royer CA, Germain P, Bourguet W. (2010) A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor. Nat Struct Mol Biol, 17 (7): 801-7. [PMID:20543827]
40. Leid M, Kastner P, Chambon P. (1992) Multiplicity generates diversity in the retinoic acid signalling pathways. Trends Biochem Sci, 17 (10): 427-33. [PMID:1333659]
41. Leroy P, Krust A, Zelent A, Mendelsohn C, Garnier JM, Kastner P, Dierich A, Chambon P. (1991) Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid. EMBO J, 10 (1): 59-69. [PMID:1846598]
42. Leroy P, Nakshatri H, Chambon P. (1991) Mouse retinoic acid receptor alpha 2 isoform is transcribed from a promoter that contains a retinoic acid response element. Proc Natl Acad Sci USA, 88 (22): 10138-42. [PMID:1658797]
43. Li E, Sucov HM, Lee KF, Evans RM, Jaenisch R. (1993) Normal development and growth of mice carrying a targeted disruption of the alpha 1 retinoic acid receptor gene. Proc Natl Acad Sci USA, 90 (4): 1590-4. [PMID:7679509]
44. Lin RJ, Egan DA, Evans RM. (1999) Molecular genetics of acute promyelocytic leukemia. Trends Genet, 15 (5): 179-84. [PMID:10322484]
45. Loudig O, Babichuk C, White J, Abu-Abed S, Mueller C, Petkovich M. (2000) Cytochrome P450RAI(CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism. Mol Endocrinol, 14 (9): 1483-97. [PMID:10976925]
46. Lufkin T, Lohnes D, Mark M, Dierich A, Gorry P, Gaub MP, LeMeur M, Chambon P. (1993) High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. Proc Natl Acad Sci USA, 90 (15): 7225-9. [PMID:8394014]
47. Mark M, Chambon P. (2003) Functions of RARs and RXRs in vivo: genetic dissection of the retinoid signaling pathway. Pure Appl Chem, 75: 1709-1732.
48. Mark M, Ghyselinck NB, Chambon P. (2006) Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu Rev Pharmacol Toxicol, 46: 451-80. [PMID:16402912]
49. Mattei MG, Rivière M, Krust A, Ingvarsson S, Vennström B, Islam MQ, Levan G, Kautner P, Zelent A, Chambon P. (1991) Chromosomal assignment of retinoic acid receptor (RAR) genes in the human, mouse, and rat genomes. Genomics, 10 (4): 1061-9. [PMID:1655630]
50. McKenna NJ, Lanz RB, O'Malley BW. (1999) Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev, 20 (3): 321-44. [PMID:10368774]
51. Nagy L, Thomázy VA, Shipley GL, Fésüs L, Lamph W, Heyman RA, Chandraratna RA, Davies PJ. (1995) Activation of retinoid X receptors induces apoptosis in HL-60 cell lines. Mol Cell Biol, 15 (7): 3540-51. [PMID:7791761]
52. Nicholson RC, Mader S, Nagpal S, Leid M, Rochette-Egly C, Chambon P. (1990) Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site. EMBO J, 9 (13): 4443-54. [PMID:2176152]
53. Oñate SA, Tsai SY, Tsai MJ, O'Malley BW. (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science, 270 (5240): 1354-7. [PMID:7481822]
54. Pavri R, Lewis B, Kim TK, Dilworth FJ, Erdjument-Bromage H, Tempst P, de Murcia G, Evans R, Chambon P, Reinberg D. (2005) PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell, 18 (1): 83-96. [PMID:15808511]
55. Petkovich M, Brand NJ, Krust A, Chambon P. (1987) A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature, 330 (6147): 444-50. [PMID:2825025]
56. Rochette-Egly C. (2003) Nuclear receptors: integration of multiple signalling pathways through phosphorylation. Cell Signal, 15 (4): 355-66. [PMID:12618210]
57. Rochette-Egly C, Adam S, Rossignol M, Egly JM, Chambon P. (1997) Stimulation of RAR alpha activation function AF-1 through binding to the general transcription factor TFIIH and phosphorylation by CDK7. Cell, 90 (1): 97-107. [PMID:9230306]
58. Ruberte E, Dolle P, Chambon P, Morriss-Kay G. (1991) Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development, 111 (1): 45-60. [PMID:1849812]
59. Ruberte E, Dolle P, Krust A, Zelent A, Morriss-Kay G, Chambon P. (1990) Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis. Development, 108 (2): 213-22. [PMID:2161730]
60. Ruberte E, Friederich V, Chambon P, Morriss-Kay G. (1993) Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Development, 118 (1): 267-82. [PMID:8397079]
61. Sande S, Privalsky ML. (1996) Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors. Mol Endocrinol, 10 (7): 813-25. [PMID:8813722]
62. Schüle R, Umesono K, Mangelsdorf DJ, Bolado J, Pike JW, Evans RM. (1990) Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene. Cell, 61 (3): 497-504. [PMID:2159384]
63. Smith WC, Nakshatri H, Leroy P, Rees J, Chambon P. (1991) A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter. EMBO J, 10 (8): 2223-30. [PMID:1648481]
64. Taneja R, Rochette-Egly C, Plassat JL, Penna L, Gaub MP, Chambon P. (1997) Phosphorylation of activation functions AF-1 and AF-2 of RAR alpha and RAR gamma is indispensable for differentiation of F9 cells upon retinoic acid and cAMP treatment. EMBO J, 16 (21): 6452-65. [PMID:9351827]
65. Teng M, Duong TT, Johnson AT, Klein ES, Wang L, Khalifa B, Chandraratna RA. (1997) Identification of highly potent retinoic acid receptor alpha-selective antagonists. J Med Chem, 40 (16): 2445-51. [PMID:9258350]
66. Thacher SM, Vasudevan J, Chandraratna RA. (2000) Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des, 6 (1): 25-58. [PMID:10637371]
67. Thoreau E, Arlabosse JM, Bouix-Peter C, Chambon S, Chantalat L, Daver S, Dumais L, Duvert G, Feret A, Ouvry G et al.. (2018) Structure-based design of Trifarotene (CD5789), a potent and selective RARγ agonist for the treatment of acne. Bioorg Med Chem Lett, 28 (10): 1736-1741. [PMID:29706423]
68. van der Leede BJ, Folkers GE, Kruyt FA, van der Saag PT. (1992) Genomic organization of the human retinoic acid receptor beta 2. Biochem Biophys Res Commun, 188 (2): 695-702. [PMID:1332705]
69. Vizirianakis IS, Chatzopoulou M, Bonovolias ID, Nicolaou I, Demopoulos VJ, Tsiftsoglou AS. (2010) Toward the development of innovative bifunctional agents to induce differentiation and to promote apoptosis in leukemia: clinical candidates and perspectives. J Med Chem, 53 (19): 6779-810. [PMID:20925433]
70. Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H. (1998) The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J, 17 (2): 507-19. [PMID:9430642]
71. Westin S, Rosenfeld MG, Glass CK. (2000) Nuclear receptor coactivators. Adv Pharmacol, 47: 89-112. [PMID:10582085]
72. Wong CW, Privalsky ML. (1998) Transcriptional silencing is defined by isoform- and heterodimer-specific interactions between nuclear hormone receptors and corepressors. Mol Cell Biol, 18 (10): 5724-33. [PMID:9742089]
73. Zelent A, Krust A, Petkovich M, Kastner P, Chambon P. (1989) Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature, 339 (6227): 714-7. [PMID:2544807]
74. Zhou XF, Shen XQ, Shemshedini L. (1999) Ligand-activated retinoic acid receptor inhibits AP-1 transactivation by disrupting c-Jun/c-Fos dimerization. Mol Endocrinol, 13 (2): 276-85. [PMID:9973257]
1B. Retinoic acid receptors: Retinoic acid receptor-α. Last modified on 28/03/2022. Accessed on 02/12/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=590.
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