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Isolation of a Novel Gene, CABC1, Encoding a Mitochondrial Protein That Is Highly Homologous to Yeast Activity of bc1 Complex¹

Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639 [M. I., H. A., T. M., Y. N.], and Department of Biotechnology, Graduate School of Science and Technology, Chiba University, Matsudo 271-8510 [M. I., A. A.], Japan

To search for p53 target genes throughout the human genome, we applied a cDNA microarray system using adenovirus-mediated transfer of p53 into p53-deficient U373MG (glioblastoma) cells. In this manner, we detected dozens of genes that appeared to be regulated by wild-type p53. We describe here characterization of one such gene, termed CABC1 [chaperone-activity of bc1 complex in Schizosaccharomyces pombe (ABC1)-like], which encodes a 647-amino acid peptide with significant sequence similarity to activity of bc1 complex (ABC1) in Arabidopsis thaliana and S. pombe. The CABC1 product was located in mitochondria, and colony-formation assays with cancer cell lines indicated its ability to suppress cell growth. Inhibition of CABC1 expression by transfection with antisense oligonucleotide significantly reduced the apoptotic response induced by wild-type p53. These results suggest that CABC1 may play an important role in mediating p53-inducible apoptosis through the mitochondrial pathway.

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