부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jsbmb.2006.09.009 Byline: Danielle Duma, Christine M. Jewell, John A. Cidlowski Keywords: Glucocorticoid receptor; Isoforms; Post-translational modification Abstract: Glucocorticoids regulate diverse physiological effects in virtually every organ and tissue in the body. Glucocorticoid actions are mediated through the glucocorticoid receptor (GR), a ligand-dependent transcriptional factor that activates or represses gene transcription. Since, the cloning of the human GR in 1985, research efforts have been focused on describing the mechanism of action exerted by one of the GR isoforms, GR[alpha]. However, recent studies from our lab and others have suggested that multiple isoforms of hGR are generated from one single gene and one mRNA species by the mechanisms of alternative RNA splicing and alternative translation initiation. These isoforms display diverse cytoplasm-to-nucleus trafficking patterns and distinct transcription activities. In addition, this new information predicts that each hGR protein can be subjected to a variety of post-translational modifications, such as phosphorylation, sumoylation and ubiquitination. The nature and degree of post-translational modification, as well as subcellular localization, may differentially modulate stability and function among the GR isoforms in different tissues providing an additional important mechanism for regulation of GR action. We outline the recent advances made in identifying the processes that generate and modify multiple GR isoforms and the post-translational modifications that contribute to the increasing diversity in the glucocorticoid signaling pathway. Author Affiliation: Laboratory of Signal Transduction, Molecular Endocrinology Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA Article Note: (footnote) [star] Lecture presentation at the 17th International Symposium of the Journal of Steroid Biochemistry & Molecular Biology, 'Recent Advances in Steroid Biochemistry and Molecular Biology' (Seefeld, Tyrol, Austria, 31 May-3 June 2006).