Molecular mechainism of apotosis induced by a novel RNA binding protein D8

新型RNA结合蛋白D8诱导细胞凋亡的分子机制

• 批准号: 15390100
• 负责人: AKIYAMA Tetsu
• 金额: $ 9.86万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390100/
• 关键词: RNA-binding protein; p53; TGF-b; apoptosis; Bim; KHドメイン; 標的遺伝子; ノックアウトマウス; TPA; 発現誘導

We identified and characterized a novel gene termed D8 that is involved in the induction of apoptosis and obtained the following results :1)Overexpression of D8 in tumor cell lines such as HepG2 resulted in the induction of apoptosis. Knockdown experiments using RNAi revealed that D8 is required for p53 and TGF-β-mediated induction of apoptosis2)Treatment of cells with anticancer reagents such as 5FU and adriamycin resulted in the induction of D8 expression. Knockdown of D8 inhibited 5FU-and adriamycin-induced apoptosis.3)Bim, a family member of the BH3 only family of proteins, was found to bind to the KH domain of D8. Knockdown experiments using RNAi revealed that Bim is important for D8-mediated apoptosis4)D8 was found to stabilize the Bim mRNA.5)To generate D8 knockdown mice, we established ES cell lines lacking the D8 gene.6)We found that D8 possesses three family members.

我们鉴定并鉴定了一个新的基因D8，该基因参与了细胞凋亡的诱导，并获得了以下结果：1）在肿瘤细胞系如HepG 2中过表达D8导致了细胞凋亡的诱导。使用RNAi的敲低实验揭示D8是p53和TGF-β介导的肿瘤诱导所需的。2）用抗癌试剂如5 FU和阿霉素处理细胞导致D8表达的诱导。D8的敲低抑制了5 FU和阿霉素诱导的结肠癌。3）Bim是仅BH 3蛋白家族的一个成员，被发现与D8的KH结构域结合。4）D8对Bim mRNA有稳定作用。5）为了获得D8基因敲低的小鼠，我们建立了D8基因敲低的ES细胞系。

项目成果

H.Seo: "Incorporation of DUF/FACT into chromatin enhances the accessibility of nucleosomal DNA."Biochem.Biophys.Res.Commun.. 303. 8-13 (2003)

H.Seo：“将 DUF/FACT 纳入染色质可增强核小体 DNA 的可及性。”Biochem.Biophys.Res.Commun.. 303. 8-13 (2003)

Role of a BCL9-related β-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling

• DOI: 10.1158/0008-5472.can-04-2254
• 发表时间: 2004-12-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Adachi, S;Jigami, T;Akiyama, T
• 通讯作者: Akiyama, T

DREG, a developmentally regulated G protein-coupled receptor containing two conserved proteolytic cleavage sites

• DOI: 10.1111/j.1356-9597.2004.00743.x
• 发表时间: 2004-06-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Moriguchi, T;Haraguchi, K;Akiyama, T
• 通讯作者: Akiyama, T

T.Okabe: "RICS, a novel GTPase-Activating Protein for Cdc42 and Rac1, is involved in the β-catenin-N-cadherin and NMDA receptor signaling.β"J.Biol.Chem.. 278. 9920-9927 (2003)

T.Okabe：“RICS 是 Cdc42 和 Rac1 的新型 GTP 酶激活蛋白，参与 β-catenin-N-cadherin 和 NMDA 受体信号传导。β”J.Biol.Chem.. 278. 9920-9927 (2003 ）

DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway

• DOI: 10.1038/sj.onc.1207892
• 发表时间: 2004-11-04
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Niida, A;Hiroko, T;Akiyama, T
• 通讯作者: Akiyama, T