The origin and functions of multiple human glucocorticoid receptor isoforms
- PMID: 15265776
- DOI: 10.1196/annals.1321.008
The origin and functions of multiple human glucocorticoid receptor isoforms
Abstract
Glucocorticoid hormones are necessary for life and are essential in all aspects of human health and disease. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which binds glucocorticoid hormones and regulates gene expression, cell signaling, and homeostasis. Decades of research have focused on the mechanisms of action of one isoform of GR, GRa. However, in recent years, increasing numbers of human GR (hGR) isoforms have been reported. Evidence obtained from this and other laboratories indicates that multiple hGR isoforms are generated from one single hGR gene via mutations and/or polymorphisms, transcript alternative splicing, and alternative translation initiation. Each hGR protein, in turn, is subject to a variety of posttranslational modifications, and the nature and degree of posttranslational modification affect receptor function. We summarize here the processes that generate and modify various hGR isoforms with a focus on those that impact the ability of hGR to regulate target genes. We speculate that unique receptor compositions and relative receptor proportions within a cell determine the specific response to glucocorticoids. Unchecked expression of some isoforms, for example hGRbeta, has been implicated in various diseases.
Similar articles
-
Glucocorticoid receptor isoforms generate transcription specificity.Trends Cell Biol. 2006 Jun;16(6):301-7. doi: 10.1016/j.tcb.2006.04.005. Epub 2006 May 11. Trends Cell Biol. 2006. PMID: 16697199 Review.
-
The human glucocorticoid receptor: one gene, multiple proteins and diverse responses.Steroids. 2005 May-Jun;70(5-7):407-17. doi: 10.1016/j.steroids.2005.02.006. Steroids. 2005. PMID: 15862824 Review.
-
Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes.Mol Cell. 2005 Apr 29;18(3):331-42. doi: 10.1016/j.molcel.2005.03.025. Mol Cell. 2005. PMID: 15866175
-
Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification.J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):11-21. doi: 10.1016/j.jsbmb.2006.09.009. Epub 2006 Oct 27. J Steroid Biochem Mol Biol. 2006. PMID: 17070034 Review.
-
Intracellular glucocorticoid signaling: a formerly simple system turns stochastic.Sci STKE. 2005 Oct 4;2005(304):pe48. doi: 10.1126/stke.3042005pe48. Sci STKE. 2005. PMID: 16204701 Review.
Cited by
-
Maternal obesogenic diet during pregnancy and its impact on fetal hepatic function in baboons.Obesity (Silver Spring). 2024 Oct;32(10):1910-1922. doi: 10.1002/oby.24124. Epub 2024 Aug 29. Obesity (Silver Spring). 2024. PMID: 39210592
-
Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection.Curr Hematol Malig Rep. 2024 Aug;19(4):175-185. doi: 10.1007/s11899-024-00735-w. Epub 2024 Jun 13. Curr Hematol Malig Rep. 2024. PMID: 38867099 Free PMC article. Review.
-
Glucocorticoid receptor (NR3C1) genetic polymorphisms and the outcomes of sudden sensorineural hearing loss.J Otolaryngol Head Neck Surg. 2023 Feb 12;52(1):13. doi: 10.1186/s40463-022-00601-w. J Otolaryngol Head Neck Surg. 2023. PMID: 36782309 Free PMC article.
-
Glucocorticoid Receptor β Isoform Predominates in the Human Dysplastic Brain Region and Is Modulated by Age, Sex, and Antiseizure Medication.Int J Mol Sci. 2022 Apr 29;23(9):4940. doi: 10.3390/ijms23094940. Int J Mol Sci. 2022. PMID: 35563330 Free PMC article.
-
Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects.Int J Mol Sci. 2022 Mar 30;23(7):3795. doi: 10.3390/ijms23073795. Int J Mol Sci. 2022. PMID: 35409154 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
