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Translational activation of the lck proto-oncogene

Nature volume 332, pages 171–173 (1988)Cite this article

Abstract

The lck proto-oncogene, a member of the src gene family, encodes a lymphocyte-specific protein tyrosine kinase (p56lck) that is implicated in the pathogenesis of lymphoid neoplasia1–4. We report here that 5' lck sequence elements, containing AUG codons, significantly reduce the in vivo efficiency of p56lck translation from the normal messenger RNA. This result provides a quantitative explanation for the overexpression of p56lck in two retrovirally-induced murine lymphomas that express abnormal lck transcripts from which the physiological 5' translational control region has been deleted and non AUG-containing viral sequences substituted. In contrast to other mammalian genes, most proto-oncogenes contain AUG codons 5' to the authentic initiation codon5, suggesting that cells can regulate translational start sites in these mRNAs. Abrogation of translational control may be a general mechanism of proto-oncogene activation in malignancy.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, University of Washington, Seattle, Washington, 98195, USA

    Jamey D. Marth, Kathryn E. Meier, Edwin G. Krebs & Roger M. Perlmutter

  2. Department of Biochemistry, University of Washington, Seattle, Washington, 98195, USA

    Roger M. Perlmutter

  3. Department of Pharmacology, University of Washington, Seattle, Washington, 98195, USA

    Kathryn E. Meier & Edwin G. Krebs

  4. Department of Medicine, University of Washington, Seattle, Washington, 98195, USA

    Jamey D. Marth & Roger M. Perlmutter

  5. Immunex Corporation, 51 University Street, Seattle, Washington, 98101, USA

    Robert W. Overell

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  3. Kathryn E. Meier
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  4. Edwin G. Krebs
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  5. Roger M. Perlmutter
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Marth, J., Overell, R., Meier, K. et al. Translational activation of the lck proto-oncogene. Nature 332, 171–173 (1988). https://doi.org/10.1038/332171a0

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