Analysis of proapoptotic functions of BH3-only protein BAD

BH3-only蛋白BAD的促凋亡功能分析

• 批准号: 15603004
• 负责人: ADACHI Masaaki
• 金额: $ 2.3万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-15603004/
• 关键词: BH-3 only protein; apoptosis; mitochondria; phosphorylation; TOF-Mass; chaperone; BH3-only蛋白; Akt; アノイキス

Most Bcl-2 family members are targeted to the mitochondria through their carboxyl terminal hydrophobic domain. A pro-apoptotic B113-only protein BAD is targeted to the mitochondria, although it has no hydrophobic tail. Mitochondrial translocation is believed to be a crucial event of BAD-mediated apoptosis, but the targeting mechanism is less clear. In this project, we demonstrate that intracellular localization of extrinsic GFP-BAD varied in transfected cell lines, i.e., cytoplasmic localization or mitochondrial accumulation. Interestingly, though GFP-BAD was dispersed throughout the cytoplasm and the nucleus, co-transfection with Bcl-xL recruited it to the mitochondria without any apoptotic signals. In contrast, co-transfection of GFP-BAD with the mutant Bcl-xL lacking hydrophobic c-terminus (Bcl-xLΔC) could not recruit BAD to the mitochondria. TOF-mass analysis of BAD-associating proteins fished Bcl-xL and 14-3-3 abundantly. Importantly, endogeneous BAD proteins mostly retained at the mitochondria in human oral squamous cell carcinoma SAS cells, and that was firmly interfered by the Bcl-xLΔC overexpression. These data indicate that Bcl-xL can recruit BAD to the mitochondria, and this process appears to occur independently of apoptotic signals.

大多数Bcl-2家族成员通过其羧基末端疏水结构域靶向线粒体。促凋亡的仅B113蛋白质不良针对线粒体，尽管它没有疏水性尾巴。线粒体易位被认为是降低凋亡的至关重要的事件，但靶向机制尚不清楚。在这个项目中，我们证明了外部GFP-BAD的细胞内定位在转染的细胞系中有所不同，即细胞质定位或线粒体积累。有趣的是，尽管GFP-BAD分散在整个细胞质和核中，但与BCL-XL共转染了其在没有任何凋亡信号的情况下募集到线粒体。相反，GFP-BAD与缺乏疏水C末端（BCL-XLΔC）的突变体BCL-XL共转染不能募集对线粒体不利。绝对对不良缔合蛋白捕获的BCL-XL和14-3-3的TOF-MAS分析。重要的是，内源性不良蛋白主要保留在人口腔鳞状细胞癌SAS细胞中，这首先被BCl-XLΔC过表达干扰。这些数据表明BCL-XL可以募集不良的线粒体，并且此过程似乎独立于凋亡信号。

项目成果

Synergistic effect of histone deacetylase inhibitors FK228 and m-Carboxycinnamic Acid Bis-Hydroxamide with proteasome inhibitors PSI and PS-341 against gastrointestinal adenocarcinoma cell

组蛋白脱乙酰酶抑制剂 FK228 和间羧肉桂酸双羟酰胺与蛋白酶体抑制剂 PSI 和 PS-341 对胃肠道腺癌细胞的协同作用

• 发表时间: 2004
• 期刊: Clin. Cancer Res. 10
• 作者: Adachi M;Zhang YB;Zhao XD;Minami T;Kawamura R;Hinoda Y;Imai K.
• 通讯作者: Imai K.

Synergistic effect of FK228 and CBHA with proteasome inhibitors PSI and PS-341 against gastrointestinal adenocarcinoma cells.

FK228 和 CBHA 与蛋白酶体抑制剂 PSI 和 PS-341 对胃肠道腺癌细胞的协同作用。

• 发表时间: 2004
• 期刊: Clin Cancer Res 10
• 作者: Adachi M;Zhang YB;Zhao XD;Minami T;Kawamura R;Hinoda Y;Imai K.;Masaaki Adachi
• 通讯作者: Masaaki Adachi

Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis

• DOI: 10.1038/sj.cdd.4401686
• 发表时间: 2006-01-01
• 期刊: CELL DEATH AND DIFFERENTIATION
• 影响因子: 12.4
• 作者: Zhang, Y;Adachi, M;Imai, K
• 通讯作者: Imai, K

NSAIDを利用した癌治療用組成物

使用 NSAID 治疗癌症的组合物

• 发表时间: 2004

Mutation of BAD within the BH3 domain impairs its phosphorylation-mediated regulation

• DOI: 10.1016/s0014-5793(03)00915-3
• 发表时间: 2003-09-11
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Adachi, M;Zhang, YB;Imai, K
• 通讯作者: Imai, K