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The human glucocorticoid receptor: one gene, multiple proteins and diverse responses.
Steroids. 2005 May-Jun; 70(5-7):407-17.S

Abstract

Glucocorticoids are a vital class of endogenous steroid hormones that regulate essential biological processes including growth, development, metabolism, behavior and apoptosis. Most, if not all, of these actions are thought to be mediated through the glucocorticoid receptor. The exact mechanisms of how one hormone, via one receptor, modulates such diverse biological functions are largely unknown. However, recent studies from our lab and others have suggested that a contribution for the diversity results from multiple isoforms of the glucocorticoid receptor that result from alternative RNA splicing and translation initiation of the glucocorticoid receptor mRNA. Additionally, each isoform is subject to several post-translational modifications, including phosphorylation, ubiquitination and sumoylation, which have been shown to modulate the receptor protein stability and/or function. Together these data provide potentially diverse mechanisms to establish cell type specific regulation of gene expression by a single transcription factor. Here, we summarize the recent advances and processes that generate these receptor isoforms and these post-translational modifications. We speculate that the composition and proportion of individual isoforms expressed in particular cellular contexts account for the diverse effects of glucocorticoid hormones.

Authors+Show Affiliations

Molecular Endocrinology Group, The Laboratory of Signal Transduction, National Institute of Environmental Health Sciences (NIEHS)/NIH, DHHS, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

15862824

Citation

Zhou, Junguo, and John A. Cidlowski. "The Human Glucocorticoid Receptor: One Gene, Multiple Proteins and Diverse Responses." Steroids, vol. 70, no. 5-7, 2005, pp. 407-17.
Zhou J, Cidlowski JA. The human glucocorticoid receptor: one gene, multiple proteins and diverse responses. Steroids. 2005;70(5-7):407-17.
Zhou, J., & Cidlowski, J. A. (2005). The human glucocorticoid receptor: one gene, multiple proteins and diverse responses. Steroids, 70(5-7), 407-17.
Zhou J, Cidlowski JA. The Human Glucocorticoid Receptor: One Gene, Multiple Proteins and Diverse Responses. Steroids. 2005 May-Jun;70(5-7):407-17. PubMed PMID: 15862824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The human glucocorticoid receptor: one gene, multiple proteins and diverse responses. AU - Zhou,Junguo, AU - Cidlowski,John A, PY - 2005/5/3/pubmed PY - 2005/9/21/medline PY - 2005/5/3/entrez SP - 407 EP - 17 JF - Steroids JO - Steroids VL - 70 IS - 5-7 N2 - Glucocorticoids are a vital class of endogenous steroid hormones that regulate essential biological processes including growth, development, metabolism, behavior and apoptosis. Most, if not all, of these actions are thought to be mediated through the glucocorticoid receptor. The exact mechanisms of how one hormone, via one receptor, modulates such diverse biological functions are largely unknown. However, recent studies from our lab and others have suggested that a contribution for the diversity results from multiple isoforms of the glucocorticoid receptor that result from alternative RNA splicing and translation initiation of the glucocorticoid receptor mRNA. Additionally, each isoform is subject to several post-translational modifications, including phosphorylation, ubiquitination and sumoylation, which have been shown to modulate the receptor protein stability and/or function. Together these data provide potentially diverse mechanisms to establish cell type specific regulation of gene expression by a single transcription factor. Here, we summarize the recent advances and processes that generate these receptor isoforms and these post-translational modifications. We speculate that the composition and proportion of individual isoforms expressed in particular cellular contexts account for the diverse effects of glucocorticoid hormones. SN - 0039-128X UR - https://www.unboundmedicine.com/medline/citation/15862824/The_human_glucocorticoid_receptor:_one_gene_multiple_proteins_and_diverse_responses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-128X(05)00037-1 DB - PRIME DP - Unbound Medicine ER -