Retinol Research Today is a free monthly online journal that collates and summarizes the latest research about Retinol, including details on vitamin a, uses, wrinkle treatment, anti-aging. | ||||||||
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Phosphorylation of the retinoid x receptor at the omega loop, modulates the expression of retinoic-acid-target genes with a promoter context specificity.Bruck N, Bastien J, Bour G, Tarrade A, Plassat JL, Bauer A, Adam-Stitah S, Rochette-Egly C Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM /ULP, BP 10142, 67404 Illkirch Cedex, France. The retinoid response is mediated by two classes of nuclear receptors, the retinoic acid receptors (RARalpha, beta, and gamma) and the retinoid X receptors (RXRalpha, beta, and gamma) which act as ligand-dependent heterodimeric RAR/RXR transcription activators. Like most transcription factors, RARs and RXRs are regulated by phosphorylation processes. Here, we report that stress agents induce RXRalpha phosphorylation, subsequently to the activation of the stress-activated protein kinases cascade (JNKs). This phosphorylation process concerns three residues located in the N-terminal AF-1 domain of RXRalpha and one located in the omega loop of the Ligand Binding Domain. To decipher how stress-induced RXRalpha phosphorylation influences the transcription of RA-target genes, we used a ribotoxic stress agent, anisomycin, which activates signaling kinases without promoting DNA or protein damages, at subinhibitory concentrations. Taking advantage of vectors expressing recombinant RXRalpha mutated at its phosphorylation sites and of F9 cell lines re-expressing the same RXRalpha mutants in an RXRalpha null background, we provide evidence that stress signaling modulates RAR/RXRalpha-mediated transcription, through the phosphorylation of RXRalpha at the residue located in the Omega loop, in a promoter context-dependent manner. Published 25 July 2005 in Cell Signal, 17(10): 1229-39.
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