FTE-1, A V-FOS TRANSFORMATION EFFECTOR GENE, ENCODES THE MAMMALIAN HOMOLOG 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 almost-equal-to 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.