Activated c-raf-1 gene from human stomach cancer

K. Shimizu, Y. Nakatsu, M. Oh-uchida, S. Nomoto, M. Sekiguchi

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Abstract

We previously isolated a novel human transforming sequence from a primary stomach cancer and identified the gene as an activated version of the c-raf-1 gene which is the human homologue of v-raf, a viral oncogene encoding a serine/threonine-specific protein kinase. Of 57 kbp of the human sequence isolated, a region of 40 kbp was found to be the minimum functional unit for the transforming activity, because a cosmid clone harboring this region was capable of inducing foci upon transfection. The size of the transcript of the transforming c-raf-1 gene was estimated to be about 2.8kb. Analyses of cDNA clones of this gene revealed that the gene was generated by substitution of the 5'-sequence (exons 1-5) of the normal c-raf-1 gene with an unrelated human sequence. We identified a region in the genomic clone where the rearrangement had occurred. The rearranged EcoRI fragment was detected in all the primary transformants obtained from two independent transfections, suggesting that the recombination had occurred in the primary cancer. The substituted cDNA sequence is composed of an open reading frame, which joins to exon 6 of the c-raf-1 gene in an in-phase manner. The substituted open reading frame encodes an extremely hydrophobic polypeptide. Thus, the putative product of the transforming gene seems to have a hydrophobic stretch ahead of the ser/thr-protein kinase domain of the c-raf-1 gene product. These results suggest that the truncation or replacement of the amino-terminal domain of the c-raf-1 protein leads to constitutive activation of the protein kinase residing in the downstream domain.

Original languageEnglish
Pages (from-to)2140-2146
Number of pages7
JournalJapanese Journal of Cancer and Chemotherapy
Volume14
Issue number6 Pt 2
Publication statusPublished - Jun 1 1987
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Shimizu, K., Nakatsu, Y., Oh-uchida, M., Nomoto, S., & Sekiguchi, M. (1987). Activated c-raf-1 gene from human stomach cancer. Japanese Journal of Cancer and Chemotherapy, 14(6 Pt 2), 2140-2146.