Molecular mechanism and physiological role of FLASH with pleiotropic activities

具有多效活性的FLASH的分子机制和生理作用

• 批准号: 22370052
• 负责人: YONEHARA Shin
• 金额: $ 11.81万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22370052/
• 关键词: 細胞周期; 転写; 細胞分化; ES細胞; Ars2; CoREST複合体; LSD1

FLASH has been shown to be required for replication-dependent histone transcription and S phase progression. We showed that FLASH is involved in transcriptional regulation through modulating histone methylation by directly interacting to histone lysine-specific demethylase 1 (LSD1) and corepressor of REST 1 (CoREST1) in the CoREST1 complex. We also showed that induced knockout of FLASH does not affect proliferation of diploid fibroblasts and ES cells, and FLASH was shown to be dispensable for ES cells to differentiate into mesoderm, endoderm, and trophoblast. FLASH might be required for cell-cycle progression specifically in transformed cells

FLASH已被证明是复制依赖性组蛋白转录和S期进展所必需的。我们发现FLASH通过直接与组蛋白赖氨酸特异性去甲基化酶1（LSD 1）和CoREST 1复合物中的REST 1辅阻遏物（CoREST 1）相互作用来调节组蛋白甲基化，从而参与转录调控。我们还发现，诱导敲除FLASH不影响二倍体成纤维细胞和ES细胞的增殖，并且FLASH被证明有利于ES细胞分化为中胚层、内胚层和滋养层。FLASH可能是细胞周期进程所必需的，特别是在转化细胞中

项目成果

Fas deficiency in mice with the Balb/c background induces blepharitis with allergic inflammation and hyper-IgE production in conjunction with severe autoimmune disease.

Balb/c 背景小鼠的 Fas 缺乏会诱发伴有过敏性炎症的睑缘炎和高 IgE 产生，并伴有严重的自身免疫性疾病。

• DOI: 10.1093/intimm/dxs109
• 发表时间: 2013
• 期刊: Int Immunol
• 影响因子: 4.4
• 作者: S. Nishimura;T. Shuku and K. Fujisawa;篠崎文夏;Takahashi S
• 通讯作者: Takahashi S

Bim regulates B-cell receptor-mediated apoptosis in the presence of CD40 signaling in CD40-pre-activated splenic B cells differentiating into plasma cells

Bim 在 CD40 预激活的脾 B 细胞分化为浆细胞的 CD40 信号存在下调节 B 细胞受体介导的细胞凋亡

• 发表时间: 2012
• 期刊: Int Immunol
• 影响因子: 4.4
• 作者: Gao Y;Kazama H and Yonehara S
• 通讯作者: Kazama H and Yonehara S

Apoptosis and Disorders : Allergic Blepharitis Associated with Hyper-Production of IgE in Balb/c Fas Knockout Mouse

细胞凋亡和疾病：Balb/c Fas 基因敲除小鼠中与 IgE 过度产生相关的过敏性睑缘炎

• 发表时间: 2011
• 作者: Rieko Kojima;et al;Shin Yonehara
• 通讯作者: Shin Yonehara

Protease Activity of Procaspase-8 Is Essential for Cell Survival by Inhibiting Both Apoptotic and Nonapoptotic Cell Death Dependent on Receptor-interacting Protein Kinase 1 (RIP1) and RIP3

• DOI: 10.1074/jbc.m112.419747
• 发表时间: 2012-11-30
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kikuchi, Mina;Kuroki, Shunsuke;Yonehara, Shin
• 通讯作者: Yonehara, Shin

Identification of a mechanism that couples multisite phosphorylation of Yes-Associated Protein (YAP) with transcriptional coactivation and regulation of aooptosis

鉴定将 Yes 相关蛋白 (YAP) 的多位点磷酸化与转录共激活和凋亡调节相结合的机制

• 发表时间: 2012
• 期刊: J Biol Chem
• 影响因子: 4.8
• 作者: Lee KK;Yonehara S
• 通讯作者: Yonehara S