Luo X, Budihardjo I, Zou H, Slaughter C, Wang X
Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA.
Cell. 1998 Aug 21;94(4):481-90. doi: 10.1016/s0092-8674(00)81589-5.
We report here the purification of a cytosolic protein that induces cytochrome c release from mitochondria in response to caspase-8, the apical caspase activated by cell surface death receptors such as Fas and TNF. Peptide mass fingerprinting identified this protein as Bid, a BH3 domain-containing protein known to interact with both Bcl2 and Bax. Caspase-8 cleaves Bid, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Immunodepletion of Bid from cell extracts eliminated the cytochrome c releasing activity. The cytochrome c releasing activity of Bid was antagonized by Bcl2. A mutation at the BH3 domain diminished its cytochrome c releasing activity. Bid, therefore, relays an apoptotic signal from the cell surface to mitochondria.
我们在此报告一种胞质蛋白的纯化，该蛋白可响应半胱天冬酶-8（由Fas和TNF等细胞表面死亡受体激活的顶端半胱天冬酶）诱导细胞色素c从线粒体释放。肽质量指纹图谱鉴定该蛋白为Bid，一种已知与Bcl2和Bax相互作用的含BH3结构域的蛋白。半胱天冬酶-8切割Bid，其COOH末端部分转移至线粒体，在那里触发细胞色素c释放。从细胞提取物中免疫去除Bid消除了细胞色素c释放活性。Bid的细胞色素c释放活性被Bcl2拮抗。BH3结构域的突变降低了其细胞色素c释放活性。因此，Bid将凋亡信号从细胞表面传递至线粒体。
