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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References
Gronemeyer, H. & Laudet, V. Protein Profile 2, 1173–1308 (1985).
Chambon, P. FASEB J. (in the press).
Kurokawa, R. et al. Nature 371, 528–531 (1994).
Forman, B. M., Umesono, K., Chen, J. & Evans, R. M. Cell 81, 541–550 (1995).
Mangelsdorf, D. J. & Evans, R. M. Cell 83, 835–850 (1995).
Lanotte, M. et al. Blood 77, 1080–1086(1991).
Warrel, R. P. et al. N. Engl. J. Med. 329, 177–189 (1993).
Grignani, F. et al. Blood 83, 10–25 (1994).
Lavau, C. & Dejean, A. Leukemia 8, 1615–1621 (1994).
Dyck, J. A. et al. Cell 76, 333–343 (1994).
Weis, K. et al. Cell 76, 345–358 (1994).
Koken, M. H. et al. EMBO J. 13, 1073–1083 (1994).
Chen, J-Y. et al. EMBO J. 14, 1187–1197 (1995).
Lehmann, J. M. et al. Science 258, 1944–1946 (1992).
Roy, B., Taneja, R. & Chambon, P. Mol. Cell. Biol. 15, 6481–6487 (1995).
Taneja, R. et al. Proc. Natl Acad. Sci. USA 93, 6197–6202 (1996).
Grignani, F. et al. Cell 74, 423–431 (1993).
Valcarcel, R., Holz, H., Jiminez, C. G., Barettino, D. & Stunnenberg, H. G. Genes Dev. 8, 3068–3079 (1994).
Dey, A., Minucci, S. & Ozato, K. Mol. Cell. Biol. 14, 8191–8201 (1994).
Kersten, S., Dawson, M. I., Lewis, B. A. & Noy, N. Biochemistry 35, 3816–3824 (1996).
Apfel, R. et al. J. Biol. Chem. 270, 30765–30772 (1995).
Durand, B. et al. Cell 71, 73–85 (1992).
Blanco, J. C. G. et al. Genes to Cells 1, 209–211 (1996).
Clifford, J. et al. EMBO J. (in the press).
Nagy, L. et al. Mol. Cell. Biol. 15, 3540–3551 (1995).
Mueller, P. R. & Wold, B. Science 246, 780–786 (1989).
Garrity, P. A. & Wold, B. J. Proc. Natl Acad. Sci. USA 89, 1021–1025 (1992).
Nagpal, S., Friant, S., Nakshatri, H. & Chambon, P. EMBO J. 12, 2349–2360 (1993).
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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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DOI: https://doi.org/10.1038/382819a0
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