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Mol Cell Biol
1997 Feb 01;172:644-55. doi: 10.1128/MCB.17.2.644.
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Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression.
Minucci S
,
Leid M
,
Toyama R
,
Saint-Jeannet JP
,
Peterson VJ
,
Horn V
,
Ishmael JE
,
Bhattacharyya N
,
Dey A
,
Dawid IB
,
Ozato K
.
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Retinoic acid receptor (RAR) and retinoid X receptor (RXR) form heterodimers and regulate retinoid-mediated gene expression. We studied binding of RXR- and RAR-selective ligands to the RXR-RAR heterodimer and subsequent transcription. In limited proteolysis analyses, both RXR and RAR in the heterodimer bound their respective ligands and underwent a conformational change in the presence of a retinoic acid-responsive element. In reporter analyses, the RAR ligand (but not the RXR ligand), when added singly, activated transcription, but coaddition of the two ligands led to synergistic activation of transcription. This activation required the AF-2 domain of both RXR and RAR. Genomic footprinting analysis was performed with P19 embryonal carcinoma cells, in which transcription of the RARbeta gene is induced upon retinoid addition. Paralleling the reporter activation data, only the RAR ligand induced in vivo occupancy of the RARbeta2 promoter when added singly. However, at suboptimal concentrations of RAR ligand, coaddition of the RXR ligand increased the stability of promoter occupancy. Thus, liganded RXR and RAR both participate in transcription. Finally, when these ligands were tested for teratogenic effects on zebra fish and Xenopus embryos, we found that coadministration of the RXR and RAR ligands caused more severe abnormalities in these embryos than either ligand alone, providing biological support for the synergistic action of the two ligands.
Allan,
Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation.
1992, Pubmed
Allan,
Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation.
1992,
Pubmed
Allan,
Ligand-dependent conformational changes in the progesterone receptor are necessary for events that follow DNA binding.
1992,
Pubmed
Allegretto,
Transactivation properties of retinoic acid and retinoid X receptors in mammalian cells and yeast. Correlation with hormone binding and effects of metabolism.
1993,
Pubmed
Allenby,
Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids.
1993,
Pubmed
Angulo,
Characterization of the sequences of the human cytomegalovirus enhancer that mediate differential regulation by natural and synthetic retinoids.
1996,
Pubmed
Apfel,
Enhancement of HL-60 differentiation by a new class of retinoids with selective activity on retinoid X receptor.
1995,
Pubmed
Barettino,
Characterization of the ligand-dependent transactivation domain of thyroid hormone receptor.
1994,
Pubmed
Bhat,
Conformational changes of human beta 1 thyroid hormone receptor induced by binding of 3,3',5-triiodo-L-thyronine.
1993,
Pubmed
Blanco,
Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR.
1996,
Pubmed
Brooks,
Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells induced by retinoic acid receptor- and retinoid X receptor-selective retinoic acid analogs.
1996,
Pubmed
Chambon,
A decade of molecular biology of retinoic acid receptors.
1996,
Pubmed
Chen,
Two distinct actions of retinoid-receptor ligands.
1996,
Pubmed
Chen,
A transcriptional co-repressor that interacts with nuclear hormone receptors.
1995,
Pubmed
Clifford,
RXRalpha-null F9 embryonal carcinoma cells are resistant to the differentiation, anti-proliferative and apoptotic effects of retinoids.
1996,
Pubmed
Davis,
Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.
1994,
Pubmed
Dey,
Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.
1992,
Pubmed
Durand,
Activation function 2 (AF-2) of retinoic acid receptor and 9-cis retinoic acid receptor: presence of a conserved autonomous constitutive activating domain and influence of the nature of the response element on AF-2 activity.
1994,
Pubmed
,
Xenbase
Durston,
Retinoic acid causes an anteroposterior transformation in the developing central nervous system.
1989,
Pubmed
,
Xenbase
Forman,
Unique response pathways are established by allosteric interactions among nuclear hormone receptors.
1995,
Pubmed
Forman,
Identification of a nuclear receptor that is activated by farnesol metabolites.
1995,
Pubmed
Fritsch,
A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain.
1992,
Pubmed
Glass,
Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers.
1994,
Pubmed
Heyman,
9-cis retinoic acid is a high affinity ligand for the retinoid X receptor.
1992,
Pubmed
Horn,
RAR and RXR selective ligands cooperatively induce apoptosis and neuronal differentiation in P19 embryonal carcinoma cells.
1996,
Pubmed
Hörlein,
Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor.
1995,
Pubmed
Kastner,
Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life?
1995,
Pubmed
Keidel,
Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping.
1994,
Pubmed
Kersten,
Individual subunits of heterodimers comprised of retinoic acid and retinoid X receptors interact with their ligands independently.
1996,
Pubmed
Kliewer,
Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors.
1992,
Pubmed
Kruyt,
A cyclic AMP response element is involved in retinoic acid-dependent RAR beta 2 promoter activation.
1992,
Pubmed
Kurokawa,
Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding.
1994,
Pubmed
Kurokawa,
Polarity-specific activities of retinoic acid receptors determined by a co-repressor.
1995,
Pubmed
La Vista-Picard,
The receptor-DNA complex determines the retinoid response: a mechanism for the diversification of the ligand signal.
1996,
Pubmed
Leblanc,
9-cis retinoic acid signaling: changing partners causes some excitement.
1995,
Pubmed
Lehmann,
Retinoids selective for retinoid X receptor response pathways.
1992,
Pubmed
Leid,
Ligand-induced alteration of the protease sensitivity of retinoid X receptor alpha.
1994,
Pubmed
Leng,
Ligand-dependent conformational changes in thyroid hormone and retinoic acid receptors are potentially enhanced by heterodimerization with retinoic X receptor.
1993,
Pubmed
Leng,
Mouse retinoid X receptor contains a separable ligand-binding and transactivation domain in its E region.
1995,
Pubmed
Levin,
9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha.
1992,
Pubmed
Lotan,
Enhanced efficacy of combinations of retinoic acid- and retinoid X receptor-selective retinoids and alpha-interferon in inhibition of cervical carcinoma cell proliferation.
1995,
Pubmed
Mangelsdorf,
The nuclear receptor superfamily: the second decade.
1995,
Pubmed
Mangelsdorf,
The RXR heterodimers and orphan receptors.
1995,
Pubmed
Minucci,
Retinoid X receptor-selective ligands produce malformations in Xenopus embryos.
1996,
Pubmed
,
Xenbase
Minucci,
Retinoid receptors in transcriptional regulation.
1996,
Pubmed
Minucci,
Dominant negative retinoid X receptor beta inhibits retinoic acid-responsive gene regulation in embryonal carcinoma cells.
1994,
Pubmed
Minucci,
Retinoic acid-mediated down-regulation of Oct3/4 coincides with the loss of promoter occupancy in vivo.
1996,
Pubmed
Nagy,
Activation of retinoid X receptors induces apoptosis in HL-60 cell lines.
1995,
Pubmed
Perlmann,
A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1.
1995,
Pubmed
Rosen,
Ligand-dependent synergy of thyroid hormone and retinoid X receptors.
1992,
Pubmed
Roy,
Synergistic activation of retinoic acid (RA)-responsive genes and induction of embryonal carcinoma cell differentiation by an RA receptor alpha (RAR alpha)-, RAR beta-, or RAR gamma-selective ligand in combination with a retinoid X receptor-specific ligand.
1995,
Pubmed
Schulman,
Activation and repression by nuclear hormone receptors: hormone modulates an equilibrium between active and repressive states.
1996,
Pubmed
Simons,
Steroid binding activity is retained in a 16-kDa fragment of the steroid binding domain of rat glucocorticoid receptors.
1989,
Pubmed
Sucov,
Characterization of an autoregulated response element in the mouse retinoic acid receptor type beta gene.
1990,
Pubmed
Taneja,
Cell-type and promoter-context dependent retinoic acid receptor (RAR) redundancies for RAR beta 2 and Hoxa-1 activation in F9 and P19 cells can be artefactually generated by gene knockouts.
1996,
Pubmed
Tsai,
Molecular mechanisms of action of steroid/thyroid receptor superfamily members.
1994,
Pubmed
Valcárcel,
Retinoid-dependent in vitro transcription mediated by the RXR/RAR heterodimer.
1994,
Pubmed
Vegeto,
The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor.
1992,
Pubmed
Willy,
LXR, a nuclear receptor that defines a distinct retinoid response pathway.
1995,
Pubmed
Xiao,
Endogenous retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers are the major functional forms regulating retinoid-responsive elements in adult human keratinocytes. Binding of ligands to RAR only is sufficient for RAR-RXR heterodimers to confer ligand-dependent activation of hRAR beta 2/RARE (DR5).
1995,
Pubmed
,
Xenbase
Yang,
Efficient inhibition of activation-induced Fas ligand up-regulation and T cell apoptosis by retinoids requires occupancy of both retinoid X receptors and retinoic acid receptors.
1995,
Pubmed
Yao,
Functional ecdysone receptor is the product of EcR and Ultraspiracle genes.
1993,
Pubmed
Zhang,
Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.
1992,
Pubmed
de Thé,
Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene.
1990,
Pubmed
