Fte-1, a v-fos transformation effector gene, encodes the mammalian homologue of a yeast gene involved in protein import into mitochondria.
Revertants were isolated from v-fos-transformed rat-1 cells cotransfected with a human cDNA expression library and a selectable marker (pMEX-neo). Molecular analysis of one clone, R2.2, suggested that the revertant phenotype resulted from the disruption of a transformation effector gene by the integration of the pMEX-neo plasmid. Genomic sequences flanking the plasmid integration site were cloned and used as probes in Northern blot analyses. A probe derived from sequences 5' to the integration site hybridized to a unique 1.2-kilobase mRNA and was used to isolate a 0.9-kilobase cDNA clone (fte-1). The open reading frame of the fte-1 cDNA predicts a highly basic protein that shows a remarkable level of similarity with two genes from Saccharomyces cerevisiae. One of these yeast genes contains an unidentified open reading frame and the other, MFT1, is a gene isolated from a yeast mutant that fails to import a fusion protein into mitochondria [Garrett, J. M., Singh, K. K., Vonder Haar, R. A. & Emr, S. D. (1991) Mol. Gen. Genet. 225, 483-491]. Expression of the fte-1 gene was induced approximately 5-fold in v-fos-transformed fibroblasts, but expression was reduced in clone R2.2 and in several independent revertant clones. Transfection of R2.2 cells with fte-1 expression vectors resulted in the reacquisition of a transformed phenotype. These results demonstrate that the mammalian homologue of a gene implicated in protein import into yeast mitochondria is a v-fos transformation effector gene.
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Division of Toxicology, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics*; D002478:Cells, Cultured; D002999:Clone Cells; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D005800:Genes, Fungal; D016762:Genes, fos; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015183:Restriction Mapping; D012269:Ribosomal Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D002352:Carrier Proteins; D012333:RNA, Messenger; C031016:RPS3A protein, human; D012269:Ribosomal Proteins; C488931:Rps3a protein, rat; D004247:DNA