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Glucocorticoid Receptor Structure and Function

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Nuclear Receptors: From Structure to the Clinic

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Abstract

Glucocorticoids are essential hormones for life and among the most potent anti-inflammatory agents, which regulate most of their biological effects at the level of gene regulation by binding to the glucocorticoid receptor (GR). The phenomenon of hormone-dependent activation of the GR has extensively been exploited for the clinical evolution of small molecule selective glucocorticoid receptor modulators. Current understanding of the available structural information of the GR places a special emphasis on the importance of conformational dynamics that play a critical role in the receptor action, and how this information can be used for structure-based drug design. Recent structural analyses have highlighted how the allosteric properties of receptor binding sites associated with glucocorticoid-regulated genes influence the composition of coregulatory complexes recruited by the GR. In addition, the role of binding partner proteins as ligands for otherwise intrinsically disordered amino-terminal, activation function-1 (AF1) in affecting gene-specific regulation could begin to define a molecular map that integrates site-specific DNA, ligands, chromatin, coregulators and post-transcriptional modifications to determine the composition and function of gene-specific transcriptional regulatory complexes involving GR.

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Authors and Affiliations

  1. Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, 18509, Scranton, PA, USA

    Raj Kumar

  2. School of Medical Sciences, Programme of Cell, Developmental and Cancer Biology, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, Scotland, UK

    Iain J. McEwan

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  1. School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom

    Iain J. McEwan

  2. Department of Basic Sciences, The Commonwealth Medical College, Scranton, Pennsylvania, USA

    Raj Kumar

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Kumar, R., McEwan, I. (2015). Glucocorticoid Receptor Structure and Function. In: McEwan, I., Kumar, R. (eds) Nuclear Receptors: From Structure to the Clinic. Springer, Cham. https://doi.org/10.1007/978-3-319-18729-7_3

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