Search of novel nuclear orphan receptors for fat-soluble ligands

寻找脂溶性配体的新型核孤儿受体

• 批准号: 11460035
• 负责人: KATO Shigeaki
• 金额: $ 9.6万
• 依托单位: Institute of Molecular and Cellular Biosciences, 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11460035/
• 关键词: fat-soluble factor; vitamin D derivatives; non-steroid hormone; heterodimer; two-hybrid assay; VDR KO mice; gene promoter; double KO mice; ステロイド甲状腺ホルモン; 脂溶性ビタミンA,D; 核内レセプター; 遺伝子スーパーファミリー; ビタミンD誘導体; 標的組換え

Some fat-soluble factors in intact aminals and diet act as ligands for nuclear receptors. In the present study, tissue-specific actions of vitamin D have been sudied by VDR KO mice, which develope rickets only after weaning. Furtherrmore, those mice were crossed with RXRγ Ko mice to establish double Ko mice for VDR and RXRγ, and the mice exhibited more over phenotypes, indicating a cross-talk between vitamin A and vitamin D.Conditional VDR KO in target tissues is under trial. We also searched novel nuclear receptors and found several candidates.

完整的氨基酸和饮食中的一些脂溶因子作为核受体的配体。在目前的研究中，维生素D的组织特异性作用已被VDR KO小鼠研究，这些小鼠只在断奶后才患上软骨病。此外，将这些小鼠与RxRγKo小鼠杂交，建立了VdR和RxRγ的双Ko小鼠，这些小鼠表现出更多的表型，表明维生素A和维生素D之间存在串扰。我们还搜索了新的核受体，发现了几个候选基因。

项目成果

Kodera,Y.,Takeyama,K.,Kato,S., et al.: "Ligand-type specific interactions of peroxisome proliferator- activated receptor gamma with transcriptional coactivators"J.Biol.Chem.. 275. 33201-33204 (2000)

Kodera，Y.，Takeyama，K.，Kato，S.，等：“过氧化物酶体增殖物激活受体γ与转录共激活剂的配体型特异性相互作用”J.Biol.Chem.. 275. 33201-33204 (2000

Watanabe,M.,Yanagisawa,J.,Kato,S., et al.: "A subfamily of RNA binding DEAD-box proteins acts as an estrogen receptor α co-activator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA."EMBO J.. 20. (2001)

Watanabe, M.、Yanagisawa, J.、Kato, S. 等人：“RNA 结合 DEAD-box 蛋白的亚家族通过 N 端激活结构域 (AF-1) 作为雌激素受体 α 共激活剂与 RNA 共激活剂 SRA。”EMBO J.. 20. (2001)

Tai,H.,Kubota,N.,Kato,S.: "Involvement of unclear receptor coactivator SRC-1 in estrogen-dependent cell growth of MCF-7 cells"Biochem.Biophys.Res.Commun.. (in press). (2000)

Tai,H.,Kubota,N.,Kato,S.：“不清楚的受体辅激活剂 SRC-1 在 MCF-7 细胞雌激素依赖性细胞生长中的参与”Biochem.Biophys.Res.Commun..（出版中）。

Takeyama,K.,Kato.S.,et al.: "Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog"Mol.Cell.Biol.. 19. 1409-1055 (1999)

Takeyama,K.,Kato.S.等人：“维生素 D 类似物对维生素 D 受体与转录共激活剂的选择性相互作用”Mol.Cell.Biol.. 19. 1409-1055 (1999)

Kobayashi.Y.,Kato.S.et al.: "p300 mediates functional synergism between AF-1 and AF-2 of estrogen receptor α and β by interacting directly with the N-terminal A/B domains"J.Biol.Chem.. (in press). (2000)

Kobayashi.Y.、Kato.S.等人：“p300 通过直接与 N 端 A/B 结构域相互作用，介导雌激素受体 α 和 β 的 AF-1 和 AF-2 之间的功能协同作用”J.Biol.Chem ..（正在出版）（2000）。