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[Cancer Research 62, 2883-2889, May 15, 2002]
© 2002 American Association for Cancer Research

Molecular Biology and Genetics

p53AIP1 Regulates the Mitochondrial Apoptotic Pathway1

Koichi Matsuda, Koji Yoshida, Yoichi Taya, Kozo Nakamura, Yusuke Nakamura2 and Hirofumi Arakawa

Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639 [K. M., K. Y., Y. N., H. A.], and Department of Orthopedic Surgery, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 [K. M., K. N.], and National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045 [Y.T.], Japan

We identified recently the p53AIP1 gene, a novel p53 target that mediates p53-dependent apoptosis. In the experiments reported here, ectopic expression of p53AIP1 induced down-regulation of mitochondrial {Delta}{Psi}m and release of cytochrome c from mitochondria in human cells. Immunoprecipitation and immunostaining experiments indicated interaction between p53AIP1 and bcl-2 proteins at mitochondria. Overexpression of bcl-2 blocked the down-regulation of mitochondrial {Delta}{Psi}m and the proapoptotic activity of p53AIP1. Our results implicate p53AIP1 as a pivotal mediator of the p53-dependent mitochondrial apoptotic pathway.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2002 by the American Association for Cancer Research.