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p53AIP1 Regulates the Mitochondrial Apoptotic Pathway¹

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 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 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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