Mechanism of transcriptional regulation by nuclear receptors

核受体转录调控机制

• 批准号: 12219206
• 负责人: KATO Shigeaki
• 金额: $ 80.06万
• 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 on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12219206/
• 关键词: transcription; co-regulator; sex hormone; nuclear receptor; RNA splicing; 転写制御; 男性ホルモン受容体異変トランスジェニックマウス; 染色体ヒストンタンパク修飾酵素複合体群; 細胞周期; 染色体構造調節因子複合体群; 性ステロイドホルモン; ホルモン依存性癌; ホルモン非依存性癌; 転写共役因子群; ERα、ERβ; アンドロゲンレセプター(AR); 性ステロイドホルモン応答性; SRC-1、TI

The most of prostate and breast cancers are dependent on the actions of sex steroid hormones in tumorigenesis. The actions of sex steroid hormones are believed to be mediated through transcriptional regulations by their nuclear receptors. For hormone-dependent regulations by nuclear receptors, a number of different nuclear complexes have been identified, that include chromatin remodeling and histone modifying complexes. To understand the hormone-induced development of such reproductive organ cancers, we have tried to identify several complexes supporting the sex steroid hormone receptors. One of the receptor-interacting complexes has turned out a spliceosome complex, and this complex physically and functionally associate with the human estrogen receptor a. As this interaction was depending on the phospholiation of the ER by MAP kinase, we propose that cross-talk of estrogen and growth factor signalings in breast cancer development mediates RNA splicing control.

大多数前列腺癌和乳腺癌依赖于性类固醇激素在肿瘤发生中的作用。性类固醇激素的作用被认为是通过其核受体的转录调控介导的。对于核受体的激素依赖性调节，已经确定了许多不同的核复合物，包括染色质重塑和组蛋白修饰复合物。为了了解激素诱导的生殖器官癌症的发展，我们试图确定几种支持性类固醇激素受体的复合物。其中一个受体相互作用的复合体是剪接体复合体，该复合体在物理和功能上与人类雌激素受体a相关联。由于这种相互作用依赖于MAP激酶对内质网的磷酸化，我们提出乳腺癌发展中雌激素和生长因子信号的串扰介导RNA剪接控制。

项目成果

Murayama, A., Kim, M., Yanagisawa, J., Kato, S., et al.: "Ligand-induced transrepression by a nuclear receptor mediated by a bHLH-type activator through co-regulator switching"EMBO J.. In press. (2004)

Murayama, A.、Kim, M.、Yanagisawa, J.、Kato, S. 等人：“bHLH 型激活剂通过共调节器切换介导的核受体引起配体诱导的反式抑制”EMBO J..

Ohtake, F., Takeyama, K., Matsumoto, T., Kato.S., et al.: "Modulation of estrogen receptor signalin by association with the activated dioxin receptor"Nature. 423. 545-550 (2003)

Ohtake, F.、Takeyama, K.、Matsumoto, T.、Kato.S. 等人：“通过与激活的二恶英受体结合来调节雌激素受体信号”，《自然》。

Suzawa, M., Takada, I., Yanagisawa.J., Kato.S., et al.: "Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade"Nature Cell Biol.. 5. 224-230 (2003)

Suzawa, M.、Takada, I.、Yanagisawa.J.、Kato.S. 等人：“细胞因子通过 TAK1/TAB1/NIK 级联抑制脂肪生成和 PPAR-gamma 功能”Nature Cell Biol.. 5. 224

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)

Brain masculinisation requires androgen receptor function.

大脑男性化需要雄激素受体功能。

• 发表时间: 2004
• 期刊: Proc. Natl. Acad. Sci. USA 101
• 作者: Sato;T.;Matsumoto;T.;Kawano;H.;Watanabe;T.;Uematsu;Y.;Sekine;K.;Fukuda;T.;Aihara;K.;Krust;A.;Yamada;T.;Nakamichi;Y.;Yamamoto;Y.;Nakamura;T.;Yoshimura;K.;Yoshizawa;T.;Metzger;D.;Chambon;P.;Kato;S.
• 通讯作者: S.