Augmentation of drug-induced cell death by ER protein BRI3BP.
Augmentation of drug-induced cell death by ER protein BRI3BP.
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DOI：
10.1016/j.bbrc.2007.08.082
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发表时间：
2007-11
影响因子：
3.1
通讯作者：
T. Yamazaki;Nozomi Sasaki;M. Nishi;D. Yamazaki;Atsushi Ikeda;Y. Okuno;S. Komazaki;H. Takeshima
中科院分区：
文献类型：
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作者：
T. Yamazaki;Nozomi Sasaki;M. Nishi;D. Yamazaki;Atsushi Ikeda;Y. Okuno;S. Komazaki;H. Takeshima
为了确定内质网（ER）对细胞命运决定的贡献，我们专注于驻留在这个细胞器中的BRI 3结合蛋白（BRI 3BP）。当BRI 3BP过表达时，增加了用包括抗癌剂依托泊苷在内的药物攻击的人胚肾293 T细胞的凋亡。相反，BRI 3BP的敲低减少了药物触发的细胞凋亡。BRI 3BP过表达增强依托泊苷处理的细胞中线粒体细胞色素c释放和caspase-3活性。在依托泊苷的反应中，ER在模拟转染的细胞中重组成不规则形状的lamellae，而在BRI 3BP过表达的细胞中，没有观察到这种重组。这些观察结果表明，BRI 3BP参与ER的结构动力学并影响线粒体活力。总之，在动物细胞类型中广泛表达的BRI 3BP似乎具有促凋亡特性，并且可以增强药物诱导的凋亡。
To determine the contribution of the endoplasmic reticulum (ER) to cell fate decision, we focused on BRI3-binding protein (BRI3BP) residing in this organelle. BRI3BP, when overexpressed, augmented the apoptosis of human embryonic kidney 293T cells challenged with drugs including the anti-cancer agent etoposide. In contrast, the knockdown of BRI3BP reduced the drug-triggered apoptosis. BRI3BP overexpression enhanced both mitochondrial cytochrome c release and caspase-3 activity in etoposide-treated cells. In response to etoposide, the ER reorganized into irregularly shaped lamellae in mock-transfected cells, whereas in BRI3BP-overexpressing cells, such reorganization was not observed. These observations suggest that BRI3BP is involved in the structural dynamics of the ER and affects mitochondrial viability. Taken together, BRI3BP, widely expressed in animal cell types, seems to possess a pro-apoptotic property and can potentiate drug-induced apoptosis.