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      The Nuclear Receptor Field: A Historical Overview and Future Challenges

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          Abstract

          In this article we summarize the birth of the field of nuclear receptors, the discovery of untransformed and transformed isoforms of ligand-binding macromolecules, the discovery of the three-domain structure of the receptors, and the properties of the Hsp90-based heterocomplex responsible for the overall structure of the oligomeric receptor and many aspects of the biological effects. The discovery and properties of the subfamily of receptors called orphan receptors is also outlined. Novel molecular aspects of the mechanism of action of nuclear receptors and challenges to resolve in the near future are discussed.

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          Most cited references132

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          The HSP90 chaperone machinery

          The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of proteostasis. Recent progress has shed light on the interactions of HSP90 with its clients and co-chaperones, and on their functional implications. This opens up new avenues for the development of drugs that target HSP90, which could be valuable for the treatment of cancers and protein-misfolding diseases.
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            The steroid and thyroid hormone receptor superfamily.

            Analyses of steroid receptors are important for understanding molecular details of transcriptional control, as well as providing insight as to how an individual transacting factor contributes to cell identity and function. These studies have led to the identification of a superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid. Although animals employ complex and often distinct ways to control their physiology and development, the discovery of receptor-related molecules in a wide range of species suggests that mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.
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              Nuclear Receptors, RXR, and the Big Bang.

              Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                101633889
                42679
                Nucl Receptor Res
                Nucl Receptor Res
                Nuclear receptor research
                2314-5706
                2314-5714
                30 July 2018
                26 July 2018
                2018
                24 August 2018
                : 5
                : 101320
                Affiliations
                [1 ]Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (1428), Argentina
                [2 ]Instituto de Biología y Medicina Experimental- CONICET. Buenos Aires (1428), Argentina
                [3 ]Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA
                Author notes
                Corresponding Author: Mario D. Galigniana, mgaligniana@ 123456conicet.gov.ar
                Article
                NIHMS983134
                10.11131/2018/101320
                6108593
                30148160
                c8b38199-b860-4e43-8707-8461603d49db

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                nuclear receptor,steroid receptor,chaperones,heat-shock proteins,hsp90,transcriptional regulation

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