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The Clinical Relevance of Steroid Hormone Receptor Corepressors

Authors' Affiliation: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Rakesh Kumar, Department of Molecular and Cellular Oncology, Unit 108, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-745-3558; Fax: 713-745-3792; E-mail: rkumar{at}mdanderson.org.

Steroid hormone receptors are ligand-dependent transcription factors that control a variety of essential physiologic and developmental processes in humans. The functional activity of a steroid receptor is regulated not only by hormones but also by an array of regulatory proteins such as coactivators, corepressors, and chromatin modifiers. Contrary to an earlier notion that corepressors and coactivators exist in separate complexes, these molecules, which have apparently opposite functions, are increasingly being found in the same complex, which allows for efficient transcriptional control mechanisms. These control mechanisms are in turn regulated by an array of post-translational modifications under the influence of upstream and local signaling networks. Because the outcome of steroidal hormone receptor transcriptional complexes is measured in terms of the expression of target genes, any dysregulation of coregulator complexes perturbs normal homeostasis and could contribute to the development and maintenance of malignant phenotypes. Increasing evidence implicating steroid hormone receptors and their coregulators in various pathophysiologic conditions has elicited interest in their structure and biology. Further advances in this field of study should open up a unique window for novel targeted therapies for diseases such as cancer. Here we briefly review the clinical relevance of corepressors, with a particular focus on their role in the development of cancerous phenotypes.

Key Words: Coregulators • Cancer • Chromatin • Transcription

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