Structural basis for carcinogenesis and cancer metastasis by oncogene products

癌基因产物致癌和癌症转移的结构基础

• 批准号: 17012009
• 负责人: NUREKI Osamu
• 金额: $ 79.23万
• 依托单位: The University of Tokyo (2007-2009)Tokyo Institute of Technology (2005-2006)
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17012009/
• 关键词: がん化; がん細胞の転移; 細胞骨格再構築; 開口放出; 転写因子; 自然免疫; X線結晶構造解析; 発がん; がんの転移; 創薬; TGF-βシグナル; 細胞内ホメオスタシス; シグナル伝達; レセプター; がん遺伝子; 薬剤設計; がん細胞の浸潤; 細胞骨格再形成; 細胞膜の開口放出; 低分子量Gタンパク質; Wnt; β-catenineシグナル

To elucidate the mechanism of carcinogenesis, cancer metastasis and anti-tumor immune reaction, atomic structures of the player, the oncoproteins and anti-oncoproteins will be determined by X-ray crystallography. Based on the structures, new anti-cancer drug will be developed to achieve an efficient cancer treatment. For carcinogenesis, we focus on TGF-β signal under which many transcription regulatory molecules interplay for cellular development signal transduction. For cancer metastasis and invasion, we focus on proteins responsible for cytoskeleton reorganization and plasma membrane supply coupled with exocytosis. For innate immune reaction, we focus on Toll-like receptor (TLR) and its endogenous ligands, and on IRF transcriptional regulators acting mainly under the control of TLR to activate the transcription of proinflammatory cytokines and γ-interferon.

为了阐明机械生成，癌症转移和抗肿瘤免疫反应，玩家的原子结构将通过X射线晶体学确定。为了致癌，我们关注许多转录调节分子R细胞发育信号转导，用于癌症转移，并带有胞外病的Invaction MA膜供应。并且是内源性配体，并且在IRF转录常规上主要是在TLR的控制下激活促炎细胞因子和γ-间隙的转录。

项目成果

Structural basis for translational fidelity ensured by tRNA lysidine synthetase

tRNA 赖氨酸合成酶确保翻译保真度的结构基础

• 发表时间: 2009
• 期刊: Nature 461
• 作者: K.Nakanishi;L.Bonnefond;S.Kimura;T.Suzuki;R.Ishitani;O.Nureki.
• 通讯作者: O.Nureki.

Regulation of platelet dense granule secretion by the Ral GTPase-Exocyst pathway

Ral GTPase-Exocyst 通路对血小板致密颗粒分泌的调节

• 发表时间: 2008
• 期刊: J.Biol.Chem. 283
• 作者: M.kawato;R.Shirakawa;H.Kondo;T.Higashi;T.Ikeda;K.Okawa;S.Fukai;O.Nureki;T.Kita;H.Horiuchi
• 通讯作者: H.Horiuchi

Structural insights into the modification in the tRNA anticodon region

tRNA 反密码子区域修饰的结构见解

• 发表时间: 2007
• 作者: T.Numata;K.Nakanishi;Y.Suzuki;A.Noma;Y.Ikeuchi;T.Suzuki;R.Ishitani;O.Nureki
• 通讯作者: O.Nureki

Crystal structure of human DAAM1 formin homology 2 domain

• DOI: 10.1111/j.1365-2443.2007.01132.x
• 发表时间: 2007-11
• 期刊: Genes to Cells
• 影响因子: 2.1
• 作者: M. Yamashita;T. Higashi;S. Suetsugu;Yusuke Sato;Tomoyuki Ikeda;R. Shirakawa;T. Kita;T. Takenawa;H. Horiuchi;S. Fukai;O. Nureki

Conserved Cysteine Residues of GidA Are Essential for Biogenesis of 5-Carboxymethylaminomethyluridine at tRNA Anticodon

• DOI: 10.1016/j.str.2009.03.013
• 发表时间: 2009-05-13
• 期刊: STRUCTURE
• 影响因子: 5.7
• 作者: Osawa, Takuo;Ito, Koichi;Numata, Tomoyuki
• 通讯作者: Numata, Tomoyuki