Study on the molecular mechanism for regulation of homeostasis by the nuclear receptors

核受体调节体内平衡的分子机制研究

• 批准号: 13470215
• 负责人: TANAKA Hirotoshi
• 金额: $ 8.7万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470215/
• 关键词: GENE; TRANSCRIPTION; NUCLEIC ACID; PHYSIOLOGY; PATHOLOGY; ENDOCRINOLOGY; PHARMACOLOGY; MOLECULAR BIOLOGY; ステロイドホルモン; 転写因子; 共役因子; DNA; RNA; グルココルチコイド; 発生工学; 核内レセプター; 転写調節

Nuclear receptors are a ligand-inducible transcription factor and regulate variety of physiological functions. Among others, the glucocorticoid receptor (GR) is a receptor for adrenocorticoglucocorticoid and pharmaceutical glucocorticoids. We have shown that GR function is modulated by a number of cellular factors including redox state, hsp90, and a novel nuclear protein HEXIM1. Moreover, a novel class of synthetic glucocorticoid cortivazol elicited differential modulation of AF-1 function of the GR. This ligand-dependent modulation of AF-1 is shown to involve helix 3 and 5 of the ligand binding domain of the GR and a p160 coactivator TIF2. Concerning the biological role of HEXIM1, we performed microarray analysis for glucocorticoiid-regulated gene expression, and showed that HEXIM1 desensitizes cells to glucocorticoids via sequestration of the GR into a particular subdomain of the nucleus.

核受体是配体诱导的转录因子，并调节生理功能的种类。除其他外，糖皮质激素受体（GR）是用于肾上腺皮质葡萄糖皮质激素和药物糖皮质激素的受体。我们已经表明，GR功能受许多细胞因子的调节，包括氧化还原态，HSP90和新型的核蛋白Hexim1。此外，一类新型的合成糖皮质激素皮质激素引起了GR的AF-1功能的差异调制。 AF-1的该配体依赖性调节显示涉及GR的配体结合结构域的螺旋3和5，而P160共激活因子TIF2。关于Hexim1的生物学作用，我们对葡萄糖皮层调节的基因表达进行了微阵列分析，并表明Hexim1通过将GR隔离为特定的子域，使细胞脱敏细胞对糖皮质激素。

项目成果

Takeyuki Nishi: "Spatial redox regulation of a critical cysteine residue of NF-κB in vivo"J. Biol. Chem.. 277・46. 44548-44556 (2002)

西武之：“体内NF-κB的关键半胱氨酸残基的空间氧化还原调节”J. Biol. 277・46（2002）。

Takanori Miura: "Functional modulation of the glucocorticoid receptor and repression of NF-kB by ursodeoxycholic acid"J.Biol.Chem.. 276(50). 47371-47378 (2001)

Takanori Miura：“熊去氧胆酸对糖皮质激素受体的功能调节和 NF-kB 的抑制”J.Biol.Chem.. 276(50)。

Role of the glucocorticoid receptor for regulation of hypoxia-dependent gene expression

• DOI: 10.1074/jbc.m302581200
• 发表时间: 2003-08-29
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kodama, T;Shimizu, N;Tanaka, H
• 通讯作者: Tanaka, H

Matsumoto M., et al.: "Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats."J.Am.Soc.Nephrol.. 14・7. 1825-1832 (2003)

Matsumoto M., et al.：“钴诱导肾脏保护基因表达改善大鼠肾脏缺血性损伤。”J.Am.Soc.Nephrol.. 14・7 (2003)。

Tsunenori Kodama, et al.: "Role of the Glucocorticoid Receptor for Regulation of Hypoxia-dependent Gene Expression"J.Biol.Chem.. 278・35. 33384-33391 (2003)

Tsunenori Kodama等：“糖皮质激素受体对缺氧依赖性基因表达的调节的作用”J.Biol.Chem.. 278・35（2003）。