|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
35
|
|
pubmed:dateCreated |
2003-8-25
|
|
pubmed:abstractText |
Glucocorticoids are secreted from the adrenal glands and act as a peripheral effector of the hypothalamic-pituitary-adrenal axis, playing an essential role in stress response and homeostatic regulation. In target cells, however, it remains unknown how glucocorticoids fine-tune the cellular pathways mediating tissue and systemic adaptation. Recently, considerable evidence indicates that adaptation to hypoxic environments is influenced by glucocorticoids and there is cross-talk between hypoxia-dependent signals and glucocorticoid-mediated regulation of gene expression. We therefore investigated the interaction between these important stress-responsive pathways, focusing on the glucocorticoid receptor (GR) and hypoxia-inducible transcription factor HIF-1. Here we show that, under hypoxic conditions, HIF-1-dependent gene expression is further up-regulated by glucocorticoids via the GR. This up-regulation cannot be substituted by the other steroid receptors and is suggested to result from the interaction between the GR and the transactivation domain of HIF-1 alpha. Moreover, our results also indicate that the ligand binding domain of the GR is essential for this interaction, and the critical requirement for GR agonists suggests the importance of the ligand-mediated conformational change of the GR. Because these proteins are shown to colocalize in the distinct compartments of the nucleus, we suggest that these stress-responsive transcription factors have intimate communication in close proximity to each other, thereby enabling the fine-tuning of cellular responses for adaptation.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Steroids,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
29
|
|
pubmed:volume |
278
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
33384-91
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:12810720-Animals,
pubmed-meshheading:12810720-Anoxia,
pubmed-meshheading:12810720-Blotting, Western,
pubmed-meshheading:12810720-COS Cells,
pubmed-meshheading:12810720-Cell Nucleus,
pubmed-meshheading:12810720-DNA-Binding Proteins,
pubmed-meshheading:12810720-Dexamethasone,
pubmed-meshheading:12810720-Dose-Response Relationship, Drug,
pubmed-meshheading:12810720-Gene Expression Regulation,
pubmed-meshheading:12810720-Genes, Reporter,
pubmed-meshheading:12810720-Glucocorticoids,
pubmed-meshheading:12810720-Green Fluorescent Proteins,
pubmed-meshheading:12810720-HeLa Cells,
pubmed-meshheading:12810720-Humans,
pubmed-meshheading:12810720-Hypoxia-Inducible Factor 1,
pubmed-meshheading:12810720-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:12810720-Ligands,
pubmed-meshheading:12810720-Luminescent Proteins,
pubmed-meshheading:12810720-Microscopy, Fluorescence,
pubmed-meshheading:12810720-Nuclear Proteins,
pubmed-meshheading:12810720-Plasmids,
pubmed-meshheading:12810720-Protein Binding,
pubmed-meshheading:12810720-Protein Conformation,
pubmed-meshheading:12810720-Protein Structure, Tertiary,
pubmed-meshheading:12810720-RNA,
pubmed-meshheading:12810720-Receptors, Glucocorticoid,
pubmed-meshheading:12810720-Recombinant Fusion Proteins,
pubmed-meshheading:12810720-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12810720-Steroids,
pubmed-meshheading:12810720-Stress, Physiological,
pubmed-meshheading:12810720-Transcription Factors,
pubmed-meshheading:12810720-Transcriptional Activation,
pubmed-meshheading:12810720-Transfection,
pubmed-meshheading:12810720-Up-Regulation
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Role of the glucocorticoid receptor for regulation of hypoxia-dependent gene expression.
|
|
pubmed:affiliation |
Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 08-8639, Japan.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
