+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Generating diversity in glucocorticoid receptor signaling: mechanisms, receptor isoforms, and post-translational modifications



Generating diversity in glucocorticoid receptor signaling: mechanisms, receptor isoforms, and post-translational modifications



Hormone Molecular Biology and Clinical Investigation 3(1): 319-328



Glucocorticoids are necessary for life after birth and regulate numerous homeostatic functions in man, including glucose homeostasis, protein catabolism, skeletal growth, respiratory function, inflammation, development, behavior, and apoptosis. In a clinical setting, they are widely used as anti-inflammatory agents to control both acute and chronic inflammation. Unfortunately, owing to their broad range of physiological actions, patients treated with glucocorticoids for long periods of time experience a variety of serious side effects, including metabolic syndrome, bone loss, and psychiatric disorders including depression, mania, and psychosis. Our understanding of how one hormone or drug regulates all of these diverse processes is limited. Recent studies have shown that multiple glucocorticoid receptor isoforms are produced from one gene via combinations of alternative mRNA splicing and alternative translation initiation. These isoforms possess unique tissue distribution patterns and transcriptional regulatory profiles. Owing to variation in the N-terminal and C-terminal length of glucocorticoid receptor isoforms, different post-translational modifications including ubiquitination, phosphorylation, and sumoylation are predicted, contributing to the complexity of glucocorticoid signaling. Furthermore, increasing evidence suggests that unique glucocorticoid receptor isoform compositions within cells could determine the cell-specific response to glucocorticoids. In this review, we will outline the recent advances made in the characterization of the transcriptional activity and the selective regulation of apoptosis by the various glucocorticoid receptor isoforms.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057925625

Download citation: RISBibTeXText

PMID: 25961204

DOI: 10.1515/hmbci.2010.039


Related references

Mechanisms generating diversity in glucocorticoid receptor signaling. Annals of the new York Academy of Sciences 1179: 167-178, 2009

Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification. Journal of Steroid Biochemistry and Molecular Biology 102(1-5): 11-21, 2006

Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Molecular Cell 18(3): 331-342, 2005

Alternative splicing and post-translational modifications contribute to diverse isoforms of the epidermal growth factor receptor. Proceedings of the American Association for Cancer Research Annual Meeting 44: 437, 2003

Regulation of protease-activated receptor signaling by post-translational modifications. Iubmb Life 63(6): 403-411, 2011

Glucocorticoid receptor isoforms in human hepatocarcinoma HepG2 and SaOS-2 osteosarcoma cells: presence of glucocorticoid receptor alpha in mitochondria and of glucocorticoid receptor beta in nucleoli. International Journal of Biochemistry and Cell Biology 37(12): 2544-2558, 2005

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor. Journal of Biological Chemistry 292(24): 10153-10168, 2017

Glucocorticoid receptor translational isoforms underlie maturational stage-specific glucocorticoid sensitivities of dendritic cells in mice and humans. Blood 121(9): 1553-1562, 2013

Post-translational modifications of the mineralocorticoid receptor: How to dress the receptor according to the circumstances?. Journal of Steroid Biochemistry and Molecular Biology 143: 334-342, 2014

The atypical Π2β2 IGF receptor expressed in inducible c2.7 myoblasts is derived from post-translational modifications of the mouse IGF-I receptor. Growth Hormone & IGF Research 18(5): 0-423, 2008

Kainate receptor post-translational modifications differentially regulate association with 4.1N to control activity-dependent receptor endocytosis. Journal of Biological Chemistry 288(13): 8952-8965, 2013

Determinants of the heightened activity of glucocorticoid receptor translational isoforms. Molecular Endocrinology 27(9): 1577-1587, 2013

Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress. Molecular and Cellular Proteomics 13(7): 1644-1658, 2014

Selective regulation of bone cell apoptosis by translational isoforms of the glucocorticoid receptor. Molecular and Cellular Biology 27(20): 7143-7160, 2007

Post-translational glycoprotein modifications regulate colon cancer stem cells and colon adenoma progression in Apc(min/+) mice through altered Wnt receptor signaling. Journal of Biological Chemistry 289(45): 31534-31549, 2014