Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2

Anthony J Capobianco, Panayiotis Zagouras, Christine M. Blaumueller, Spyros Artavanis-Tsakonas, J. Michael Bishop

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209 Scopus citations

Abstract

The Notch genes of Drosophila melanogaster and vertebrates encode transmembrane receptors that help determine cell fate during development. Although ligands for Notch proteins have been identified, the signaling cascade downstream of the receptors remains poorly understood. In human acute lymphoblastic T-cell leukemia, a chromosomal translocation damages the NOTCH1 gene. The damage apparently gives rise to a constitutively activated version of NOTCH protein. Here we show that a truncated version of NOTCH1 protein resembling that found in the leukemic cells can transform rat kidney cells in vitro. The transformation required cooperation with the E1A oncogene of adenovirus. The transforming version of NOTCH protein was located in the nucleus. In contrast, neither wild-type NOTCH protein nor a form of the truncated protein permanently anchored to the plasma membrane produced transformation in vitro. We conclude that constitutive activation of NOTCH similar to that found in human leukemia can contribute to neoplastic transformation. Transformation may require that the NOTCH protein be translocated to the nucleus. These results sustain a current view of how Notch transduces a signal from the surface of the cell to the nucleus.

Original languageEnglish
Pages (from-to)6265-6273
Number of pages9
JournalMolecular and Cellular Biology
Volume17
Issue number11
StatePublished - Nov 1 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Capobianco, A. J., Zagouras, P., Blaumueller, C. M., Artavanis-Tsakonas, S., & Bishop, J. M. (1997). Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2. Molecular and Cellular Biology, 17(11), 6265-6273.