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  • Title: Architecture of DNA Bound RAR heterodimers.
    Author: Rochel N, Moras D.
    Journal: Subcell Biochem; 2014; 70():21-36. PubMed ID: 24962879.
    Abstract:
    Nuclear Retinoic Acid receptors (RARs) consist of three subtypes, α, β, and γ, encoded by separate genes. They function as ligand-dependent transcriptional regulators, forming heterodimers with Retinoid X receptors (RXRs). RARs mediate the effects of retinoic acid (RA), the active metabolite of Vitamin A, and regulate many biological functions such as embryonic development, organogenesis, homeostasis, vision, immune functions, and reproduction. During the two last decades, a number of in-depth structure-function relationship studies have been performed, in particular with drug design perspectives in the therapeutics for cancer, dermatology, metabolic disease, and other human diseases. Recent structural results concerning integral receptors in diverse functional states, obtained using a combination of different methods, allow a better understanding of the mechanisms involved in molecular regulation. The structural data highlight the importance of DNA sequences for binding selectivity and the role of promoter response elements in the spatial organization of the protein domains into functional complexes.
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