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Molecular cloning and characterization of the human dbl proto-oncogene: evidence that its overexpression is

D Ron1, S R Tronick, S A Aaronson

  • 1Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.

The EMBO Journal
|August 1, 1988
PubMed

Insights

The human dbl proto-oncogene encodes a protein that can transform cells. Structural changes to this proto-oncogene significantly enhance its transforming activity, suggesting a new class of oncogenes linked to the cytoskeleton.

Area of Science:

  • Molecular Biology
  • Oncogenesis
  • Cellular Biology

Background:

  • The human dbl proto-oncogene transcript was isolated and analyzed.
  • Previous work demonstrated the dbl oncogene arose from a rearrangement of proto-dbl.
  • The dbl oncogene resulted from the substitution of the 5' portion of proto-dbl with an unrelated human sequence.

Purpose of the Study:

  • To characterize the human dbl proto-oncogene and its protein product.
  • To investigate the transforming activity of proto-dbl and its relationship to the dbl oncogene.
  • To identify potential structural similarities and functional implications of proto-dbl.

Main Methods:

  • Isolation and sequencing of cDNA clones for human proto-dbl.
  • Expression of proto-dbl in COS cells and detection of the protein product using peptide antisera.
  • Transformation assays of NIH/3T3 cells with proto-dbl and the dbl oncogene under a strong promoter.
  • Bioinformatic analysis for structural similarities to known proteins.

Main Results:

  • A predicted protein of 925 amino acids was identified for proto-dbl.
  • A 115-kd protein, consistent with predictions, was detected in transfected cells.
  • Proto-dbl overexpression transformed NIH/3T3 cells, but less effectively than the dbl oncogene.
  • A 300-amino acid region in proto-dbl showed structural similarity to vimentin, containing a heptad repeat motif.

Conclusions:

  • Proto-dbl overexpression is sufficient for NIH/3T3 cell transformation.
  • Specific structural alterations enhance the transforming activity of the dbl oncogene.
  • Human proto-dbl represents a novel class of cellular oncogenes potentially associated with cytoskeletal elements.

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