Two distinct actions of retinoid-receptor ligands (original) (raw)

Nature volume 382, pages 819–822 (1996)Cite this article

Abstract

SIGNALLING by all-trans retinoic acid is mediated through RXR-RAR retinoid receptor heterodimers1,2, in which RXR has been considered to act as a transcriptionally silent partner3–5. However, we show here that in cultured NB4 (ref. 6) human acute promyelocytic leukaemia7–9 cells treated with either an RAR-α-selective agonist alone, or certain RAR-α antagonists in combination with an RXR agonist, receptor–DNA binding is induced in vivo, resulting in expression of the target genes of retinoic acid as well as acute promyelocytic leukaemia protein (PML) relocation to nuclear bodies10–12 and differentiation before apoptosis. These results indicate that RAR-α ligands can induce two separate events: one enables RXR–RAR-α heterodimers to bind to DNA in vivo and allows RXR agonists to act; the other induces transcriptional activity of RAR-α. The availability of receptor-specific synthetic retinoids that can induce distinct receptor functions has potential in extending the therapeutic repertoire of retinoids.

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Authors and Affiliations

  1. institut de Génetique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, BP 163, 67404, Illkrich Cedex, CU de Strasbourg, France
    Jia-Yang Chen, John Clifford, Pierre Chambon & Hinrich Gronemeyer
  2. Bristol-Meyers Squibb Pharmaceutical Research Institute, 100 Forest Avenue, Buffalo, New York, 14213-1091, USA
    Chris Zusi, John Starrett, David Tortolani, Jacek Ostrowski & Peter R. Reczek

Authors

  1. Jia-Yang Chen
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  2. John Clifford
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  3. Chris Zusi
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  4. John Starrett
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  5. David Tortolani
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  6. Jacek Ostrowski
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  7. Peter R. Reczek
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  8. Pierre Chambon
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  9. Hinrich Gronemeyer
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Chen, JY., Clifford, J., Zusi, C. et al. Two distinct actions of retinoid-receptor ligands.Nature 382, 819–822 (1996). https://doi.org/10.1038/382819a0

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