The receptor-DNA complex determines the retinoid response: a mechanism for the diversification of the ligand signal.
AUTOR(ES)
La Vista-Picard, N
RESUMO
To obtain insights into the principles governing the complex biological responses to retinoids, we have analyzed the ligand sensitivities of various retinoid receptor-DNA complexes. We find that different retinoid receptor heterodimers show distinct activation patterns with various response elements while a given heterodimer can be activated at different retinoic acid concentrations on different response elements. In vitro binding experiments suggest that the same retinoic acid receptor-retinoid X receptor (RAR-RXR) heterodimer can have different ligand affinities, depending on the response element it is bound to. The differential responses of a particular receptor heterodimer with various retinoic acid responsive elements can be enhanced through the use of conformationally restricted retinoids. RAR- and RXR-selective retinoids can also synergistically activate the receptor heterodimers, indicating that both partners in the heterodimer can contribute to ligand-induced transcriptional activation. However, the relative influence of the RAR or RXR partner is specific for each response element. Together, our data demonstrate that it is the receptor-DNA complex and not the receptor alone that determines the ligand response. This flexibility allows for a highly pleiotropic retinoid response. Furthermore, conformationally restricted retinoids can accentuate the differential responses and exhibit a certain degree of gene selectivity by differentially activating the RAR or RXR component in the context of a given response element.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=231410Documentos Relacionados
- Vitamin D-influenced gene expression via a ligand-independent, receptor-DNA complex intermediate.
- How hormone receptor-DNA binding affects nucleosomal DNA: the role of symmetry.
- Isolation of a thyroid hormone-responsive gene by immunoprecipitation of thyroid hormone receptor-DNA complexes.
- Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.
- Inhibition of estrogen receptor-DNA binding by the "pure" antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization.