Biology:Retinoid X receptor alpha
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Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 (nuclear receptor subfamily 2, group B, member 1) is a nuclear receptor that in humans is encoded by the RXRA gene.[1]
Function
Retinoid X receptors (RXRs) and retinoic acid receptors (RARs), are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors exert their action by binding, as homodimers or heterodimers, to specific sequences in the promoters of target genes and regulating their transcription. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcription factors.[2] In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the cytochrome P450 system genes.[3]
Interactive pathway map
Interactions
Retinoid X receptor alpha has been shown to interact with:
- BCL3,[4]
- BRD8,[5]
- CLOCK,[6]
- FXR[7]
- IGFBP3,[8]
- ITGB3BP,[9]
- LXR-β,[7]
- MyoD,[10]
- NCOA6,[11][12][13][14]
- NFKBIB,[15]
- NPAS2,[6]
- NRIP1,[16][17]
- NR4A1,[18]
- NCOA2,[19]
- NCOA3,[20]
- POU2F1,[21][22]
- PPARGC1A,[23]
- PPAR-γ,[24][25][26]
- RNF8,[27]
- RAR-α,[28][29]
- SHP,[30][31]
- TADA3L,[32]
- TBP,[33]
- TRIM24,[34][35]
- TR-β,[36][37] and
- VDR.[19][38]
See also
References
- ↑ "Nuclear receptor that identifies a novel retinoic acid response pathway". Nature 345 (6272): 224–9. May 1990. doi:10.1038/345224a0. PMID 2159111. Bibcode: 1990Natur.345..224M.
- ↑ "Entrez Gene: RXRA retinoid X receptor, alpha". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6256.
- ↑ "Retinoic acid receptor RXR-alpha - Homo sapiens (Human)". UniProt. https://www.uniprot.org/uniprot/P19793.
- ↑ "Bcl3, an IkappaB protein, as a novel transcription coactivator of the retinoid X receptor". J. Biol. Chem. 273 (47): 30933–8. 1998. doi:10.1074/jbc.273.47.30933. PMID 9812988.
- ↑ "p120 acts as a specific coactivator for 9-cis-retinoic acid receptor (RXR) on peroxisome proliferator-activated receptor-gamma/RXR heterodimers". Mol. Endocrinol. 13 (10): 1695–703. 1999. doi:10.1210/mend.13.10.0353. PMID 10517671.
- ↑ 6.0 6.1 "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. 2001. doi:10.1016/S0092-8674(01)00401-9. PMID 11439184.
- ↑ 7.0 7.1 "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Mol. Endocrinol. 9 (1): 72–85. 1995. doi:10.1210/mend.9.1.7760852. PMID 7760852.
- ↑ "Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis". J. Biol. Chem. 275 (43): 33607–13. 2000. doi:10.1074/jbc.M002547200. PMID 10874028.
- ↑ "NRIF3 is a novel coactivator mediating functional specificity of nuclear hormone receptors". Mol. Cell. Biol. 19 (10): 7191–202. 1999. doi:10.1128/mcb.19.10.7191. PMID 10490654.
- ↑ "Retinoic acid receptors and muscle b-HLH proteins: partners in retinoid-induced myogenesis". Oncogene 16 (26): 3369–78. 1998. doi:10.1038/sj.onc.1201894. PMID 9692544.
- ↑ "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. 1999. doi:10.1074/jbc.274.48.34283. PMID 10567404.
- ↑ "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Mol. Endocrinol. 15 (2): 241–54. 2001. doi:10.1210/mend.15.2.0595. PMID 11158331.
- ↑ "Hepatitis B virus X protein regulates transactivation activity and protein stability of the cancer-amplified transcription coactivator ASC-2". Hepatology 38 (5): 1258–66. 2003. doi:10.1053/jhep.2003.50451. PMID 14578865.
- ↑ "Ser-884 adjacent to the LXXLL motif of coactivator TRBP defines selectivity for ERs and TRs". Mol. Endocrinol. 16 (1): 128–40. 2002. doi:10.1210/mend.16.1.0755. PMID 11773444.
- ↑ "IkappaBbeta interacts with the retinoid X receptor and inhibits retinoid-dependent transactivation in lipopolysaccharide-treated cells". J. Biol. Chem. 273 (6): 3212–5. 1998. doi:10.1074/jbc.273.6.3212. PMID 9452433.
- ↑ "Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity". Biochemistry 42 (4): 971–9. 2003. doi:10.1021/bi020497k. PMID 12549917.
- ↑ "RIP-140 interacts with multiple nuclear receptors by means of two distinct sites". Mol. Cell. Biol. 16 (11): 6029–36. 1996. doi:10.1128/MCB.16.11.6029. PMID 8887632.
- ↑ "Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3". Cell 116 (4): 527–40. 2004. doi:10.1016/S0092-8674(04)00162-X. PMID 14980220.
- ↑ 19.0 19.1 "Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription". J. Biol. Chem. 276 (44): 40614–20. 2001. doi:10.1074/jbc.M106263200. PMID 11514567.
- ↑ "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. 1997. doi:10.1016/S0092-8674(00)80516-4. PMID 9267036.
- ↑ "Selective binding of steroid hormone receptors to octamer transcription factors determines transcriptional synergism at the mouse mammary tumor virus promoter". J. Biol. Chem. 274 (38): 26713–9. 1999. doi:10.1074/jbc.274.38.26713. PMID 10480874.
- ↑ "Functional interaction between Oct-1 and retinoid X receptor". J. Biol. Chem. 274 (27): 19103–8. 1999. doi:10.1074/jbc.274.27.19103. PMID 10383413.
- ↑ "PGC-1 functions as a transcriptional coactivator for the retinoid X receptors". J. Biol. Chem. 277 (6): 3913–7. 2002. doi:10.1074/jbc.M109409200. PMID 11714715.
- ↑ "Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha". Nucleic Acids Res. 22 (25): 5628–34. 1994. doi:10.1093/nar/22.25.5628. PMID 7838715.
- ↑ "A PPARgamma mutant serves as a dominant negative inhibitor of PPAR signaling and is localized in the nucleus". Mol. Cell. Endocrinol. 162 (1–2): 57–67. 2000. doi:10.1016/S0303-7207(00)00211-2. PMID 10854698.
- ↑ "Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors". Mol. Cell 5 (3): 545–55. 2000. doi:10.1016/S1097-2765(00)80448-7. PMID 10882139.
- ↑ "The RING finger protein, RNF8, interacts with retinoid X receptor alpha and enhances its transcription-stimulating activity". J. Biol. Chem. 279 (18): 18926–34. 2004. doi:10.1074/jbc.M309148200. PMID 14981089.
- ↑ "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. 2002. doi:10.1128/MCB.22.13.4522-4534.2002. PMID 12052862.
- ↑ "RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors". EMBO J. 11 (4): 1409–18. 1992. doi:10.1002/j.1460-2075.1992.tb05186.x. PMID 1314167.
- ↑ "The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression". Mol. Cell. Biol. 20 (1): 187–95. 2000. doi:10.1128/MCB.20.1.187-195.2000. PMID 10594021.
- ↑ "The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity". Mol. Endocrinol. 16 (9): 2065–76. 2002. doi:10.1210/me.2001-0194. PMID 12198243.
- ↑ "Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated transactivation by targeting human ADA3 coactivator". J. Biol. Chem. 277 (47): 45611–8. 2002. doi:10.1074/jbc.M208447200. PMID 12235159.
- ↑ "Interactions between the retinoid X receptor and a conserved region of the TATA-binding protein mediate hormone-dependent transactivation". Proc. Natl. Acad. Sci. U.S.A. 92 (18): 8288–92. 1995. doi:10.1073/pnas.92.18.8288. PMID 7667283. Bibcode: 1995PNAS...92.8288S.
- ↑ "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". J. Biol. Chem. 272 (18): 12062–8. 1997. doi:10.1074/jbc.272.18.12062. PMID 9115274.
- ↑ "Interactions of RXR with coactivators are differentially mediated by helix 11 of the receptor's ligand binding domain". Biochemistry 41 (8): 2500–8. 2002. doi:10.1021/bi011764+. PMID 11851396.
- ↑ "Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein". J. Biol. Chem. 272 (47): 29834–41. 1997. doi:10.1074/jbc.272.47.29834. PMID 9368056.
- ↑ "Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor". Mol. Endocrinol. 11 (6): 755–67. 1997. doi:10.1210/mend.11.6.0003. PMID 9171239.
- ↑ "Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription". J. Biol. Chem. 273 (26): 16434–41. 1998. doi:10.1074/jbc.273.26.16434. PMID 9632709.
Further reading
- "Retinoid X receptors: X-ploring their (patho)physiological functions". Cell Death Differ. 11 (Suppl 2): S126–43. December 2004. doi:10.1038/sj.cdd.4401533. PMID 15608692.
- "9-cis retinoic acid is a high affinity ligand for the retinoid X receptor". Cell 68 (2): 397–406. January 1992. doi:10.1016/0092-8674(92)90479-V. PMID 1310260.
- "Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling". Nature 355 (6359): 446–9. January 1992. doi:10.1038/355446a0. PMID 1310351. Bibcode: 1992Natur.355..446K.
- "Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling". Proc. Natl. Acad. Sci. U.S.A. 89 (4): 1448–52. February 1992. doi:10.1073/pnas.89.4.1448. PMID 1311101. Bibcode: 1992PNAS...89.1448K.
- "RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors". EMBO J. 11 (4): 1409–18. April 1992. doi:10.1002/j.1460-2075.1992.tb05186.x. PMID 1314167.
- "Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein". Mol. Endocrinol. 6 (9): 1468–78. September 1992. doi:10.1210/mend.6.9.1331778. PMID 1331778.
- "A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR". Cell 66 (3): 555–61. August 1991. doi:10.1016/0092-8674(81)90018-0. PMID 1651173.
- "Nuclear receptor that identifies a novel retinoic acid response pathway". Nature 345 (6272): 224–9. May 1990. doi:10.1038/345224a0. PMID 2159111. Bibcode: 1990Natur.345..224M.
- "Sequence and characterization of a coactivator for the steroid hormone receptor superfamily". Science 270 (5240): 1354–7. 1995. doi:10.1126/science.270.5240.1354. PMID 7481822. Bibcode: 1995Sci...270.1354O.
- "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature 377 (6548): 454–7. 1995. doi:10.1038/377454a0. PMID 7566127. Bibcode: 1995Natur.377..454C.
- "Interactions between the retinoid X receptor and a conserved region of the TATA-binding protein mediate hormone-dependent transactivation". Proc. Natl. Acad. Sci. U.S.A. 92 (18): 8288–92. August 1995. doi:10.1073/pnas.92.18.8288. PMID 7667283. Bibcode: 1995PNAS...92.8288S.
- "A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1". Genes Dev. 9 (7): 769–82. April 1995. doi:10.1101/gad.9.7.769. PMID 7705655.
- "Structural determinants of nuclear receptor assembly on DNA direct repeats". Nature 375 (6528): 203–11. 1995. doi:10.1038/375203a0. PMID 7746322. Bibcode: 1995Natur.375..203R.
- "Unique response pathways are established by allosteric interactions among nuclear hormone receptors". Cell 81 (4): 541–50. 1995. doi:10.1016/0092-8674(95)90075-6. PMID 7758108.
- "Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors". Mol. Endocrinol. 9 (1): 72–85. 1995. doi:10.1210/mend.9.1.7760852. PMID 7760852.
- "Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha". Nature 375 (6530): 377–82. June 1995. doi:10.1038/375377a0. PMID 7760929. Bibcode: 1995Natur.375..377B.
- "Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor". Mol. Endocrinol. 9 (2): 243–54. February 1995. doi:10.1210/mend.9.2.7776974. PMID 7776974.
- "Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha". Nucleic Acids Res. 22 (25): 5628–34. December 1994. doi:10.1093/nar/22.25.5628. PMID 7838715.
- "Interaction of thyroid-hormone receptor with a conserved transcriptional mediator". Nature 374 (6517): 91–4. March 1995. doi:10.1038/374091a0. PMID 7870181. Bibcode: 1995Natur.374...91L.
- "NMR assignments and secondary structure of the retinoid X receptor alpha DNA-binding domain. Evidence for the novel C-terminal helix". Eur. J. Biochem. 224 (2): 639–50. September 1994. doi:10.1111/j.1432-1033.1994.00639.x. PMID 7925381.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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