| RRC ID |
41895
|
| 著者 |
Kodama T, Shimizu N, Yoshikawa N, Makino Y, Ouchida R, Okamoto K, Hisada T, Nakamura H, Morimoto C, Tanaka H.
|
| タイトル |
Role of the glucocorticoid receptor for regulation of hypoxia-dependent gene expression.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
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.
|
| 巻・号 |
278(35)
|
| ページ |
33384-91
|
| 公開日 |
2003-8-29
|
| DOI |
10.1074/jbc.M302581200
|
| PII |
S0021-9258(20)83906-4
|
| PMID |
12810720
|
| MeSH |
Animals
Blotting, Western
COS Cells
Cell Nucleus / metabolism
DNA-Binding Proteins / metabolism
Dexamethasone / pharmacology
Dose-Response Relationship, Drug
Gene Expression Regulation*
Genes, Reporter
Glucocorticoids / metabolism
Green Fluorescent Proteins
HeLa Cells
Humans
Hypoxia*
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Ligands
Luminescent Proteins / metabolism
Microscopy, Fluorescence
Nuclear Proteins / metabolism
Plasmids / metabolism
Protein Binding
Protein Conformation
Protein Structure, Tertiary
RNA / metabolism
Receptors, Glucocorticoid / physiology*
Recombinant Fusion Proteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Steroids / metabolism
Stress, Physiological
Transcription Factors / metabolism
Transcriptional Activation
Transfection
Up-Regulation
|
| IF |
4.238
|
| 引用数 |
75
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
