| Site-specific phosphorylation induces functionally active conformation in the intrinsically disordered N-terminal activation function (AF1) domain of the glucocorticoid receptor. | |
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MedLine Citation:
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PMID: 19841061 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Intrinsically disordered (ID) regions are disproportionately higher in cell signaling proteins and are predicted to have much larger frequency of phosphorylation sites than ordered regions, suggesting an important role in their regulatory capacity. In this study, we show that AF1, an ID activation domain of the glucocorticoid receptor (GR), adopts a functionally folded conformation due to its site-specific phosphorylation by p38 mitogen-activated protein kinase, which is involved in apoptotic and gene-inductive events initiated by the GR. Further, we show that site-specific phosphorylation-induced secondary and tertiary structure formation specifically facilitates AF1's interaction with critical coregulatory proteins and subsequently its transcriptional activity. These data demonstrate a mechanism through which ID activation domain of the steroid receptors and other similar transcription factors may adopt a functionally active conformation under physiological conditions. |
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Authors:
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Anna M S Garza; Shagufta H Khan; Raj Kumar |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-16 Completed Date: 2010-01-14 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 220-30 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals CREB-Binding Protein / metabolism Cell Line Cercopithecus aethiops Humans Nuclear Receptor Coactivator 1 / metabolism Phosphorylation Protein Folding Protein Structure, Secondary Protein Structure, Tertiary Receptors, Glucocorticoid / chemistry, metabolism* Recombinant Proteins / chemistry TATA-Box Binding Protein / metabolism Transcription, Genetic p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, chemistry, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK058829/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Glucocorticoid; 0/Recombinant Proteins; 0/TATA-Box Binding Protein; EC 2.3.1.48/CREB-Binding Protein; EC 2.3.1.48/Nuclear Receptor Coactivator 1; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
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