論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | COS-7(RCB0539) |