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Subnuclear Trafficking of Glucocorticoid Receptors

General Mechanisms and Specific Recruitment to a Unique Target Site by Tethering to a DNA-Bound POU Domain Protein

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Gene Engineering in Endocrinology

Part of the book series: Contemporary Endocrinology ((COE,volume 22))

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Abstract

All members of the steroid hormone/nuclear receptor superfamily function as transcriptional regulatory proteins and have the capacity to interact specifically with select target genes (1). Although many mechanistic aspects of the nuclear receptor—regulated transcription have been elucidated over the past 15 yr (2), our understanding of how this process is efficiently orchestrated in a crowded nucleus remains limited. How do receptors locate their target sites within native chromatin? Are nuclear receptors free to “diffuse” throughout the nucleus in search of high-affinity sites, or is their trafficking restricted through a distinct set of subnuclear compartments? Which factors regulate receptor trafficking within the nucleus? This chapter focuses initially on global mechanisms of steroid receptor subcellular trafficking with a particular emphasis on nucleo-cytoplasmic shuttling and nuclear export of the glucocorticoid receptor (GR). Subsequently, our discussion shifts to a novel mechanism of GR transrepression in which GR recruitment to a unique target site is mediated not by specific DNA binding, but by site-specific tethering of the receptor to a DNA-bound POU domain transcription factor.

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Authors
  1. Uma R. Chandran PhD
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  2. Donald B. DeFranco PhD
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Editors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, VA, USA

    Margaret A. Shupnik PhD

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Chandran, U.R., DeFranco, D.B. (2000). Subnuclear Trafficking of Glucocorticoid Receptors. In: Shupnik, M.A. (eds) Gene Engineering in Endocrinology. Contemporary Endocrinology, vol 22. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-221-0_5

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  • DOI: https://doi.org/10.1007/978-1-59259-221-0_5

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