TY - JOUR
T1 - Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis
AU - Li, Honglin
AU - Zhu, Hong
AU - Xu, Chi Jie
AU - Yuan, Junying
N1 - Funding Information:
We thank Dr. Marc Kirschner and the members of his laboratory for helpful advice on constructing and using the small pool expression library, which was critical for the success of this project. We thank Kevin Welch, Xun Clare Zhou, and members of the Yuan laboratory for a joint effort in preparing the small pool cDNA library, which was a lot of work. We thank Dr. Arnold Greenberg for providing granzyme B; Dr. Vishva Dixit for permission to use MCF7/Fas and MCF7/Fas/Bclx L cells; Dr. Emad Alnemri for Casp9 DN; Drs. Yoshihide Tsujimoto and Xiaodong Wang for protocols and advice on preparation of mitochondria; and Dr. Zhi-Jun Lu for GST-Bax. We also thank Xun Clare Zhou, Roberto Sanchez-Olea, Suyue Wang, Louise Bergeron, and Qiang Yu for their critical reading of the manuscript. This work was supported in part by a postdoctoral fellowship from National Institute of Aging (to H. L.), a grant from the Army’s Breast Cancer Program (to J. Y.), and an American Heart Established Investigatorship (to J. Y.).
PY - 1998/8/21
Y1 - 1998/8/21
N2 - We report here that BID, a BH3 domain-containing proapoptotic Bc12 family member, is a specific proximal substrate of Casp8 in the Fas apoptotic signaling pathway. While full-length BID is localized in cytosol, truncated BID (tBID) translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. tBID induces first the clustering of mitochondria around the nuclei and release of cytochrome c independent of caspase activity, and then the loss of mitochondrial membrane potential, cell shrinkage, and nuclear condensation in a caspase-dependent fashion. Coexpression of Bclx(L) inhibits all the apoptotic changes induced by tBID. Our results indicate that BID is a mediator of mitochondrial damage induced by Casp8.
AB - We report here that BID, a BH3 domain-containing proapoptotic Bc12 family member, is a specific proximal substrate of Casp8 in the Fas apoptotic signaling pathway. While full-length BID is localized in cytosol, truncated BID (tBID) translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. tBID induces first the clustering of mitochondria around the nuclei and release of cytochrome c independent of caspase activity, and then the loss of mitochondrial membrane potential, cell shrinkage, and nuclear condensation in a caspase-dependent fashion. Coexpression of Bclx(L) inhibits all the apoptotic changes induced by tBID. Our results indicate that BID is a mediator of mitochondrial damage induced by Casp8.
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U2 - 10.1016/S0092-8674(00)81590-1
DO - 10.1016/S0092-8674(00)81590-1
M3 - Article
C2 - 9727492
AN - SCOPUS:0032555697
SN - 0092-8674
VL - 94
SP - 491
EP - 501
JO - Cell
JF - Cell
IS - 4
ER -