Isolation of a novel gene, CABC1, encoding a mitochondrial protein that is highly homologous to yeast activity of bc1 complex.
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.
Iiizumi
Megumi
M
Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Arakawa
Hirofumi
H
Mori
Toshiki
T
Ando
Akikazu
A
Nakamura
Yusuke
Y
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D004249:DNA Damage; D005656:Fungal Proteins / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008928:Mitochondria / Q000737:chemistry* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
C451061:CABC1 protein, S pombe; C099891:COQ8 protein, S cerevisiae; D005656:Fungal Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D016159:Tumor Suppressor Protein p53