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Activation of the Notch-regulated transcription factor CBF1/RBP-J kappa through the 13SE1A oncoprotein

Authors

  • S. Ansieau
  • L.J. Strobl
  • A. Leutz

Journal

  • Genes & Development

Citation

  • Genes Dev 15 (4): 380-385

Abstract

  • Signaling through the Notch pathway controls cell growth and differentiation in metazoans. Following binding of its ligands, the intracellular part of the cell surface Notch1 receptor (Notch1-IC) is released and translocates to the nucleus, where it alters the function of the DNA-binding transcription factor CBF1/RBP-Jκ. As a result, CBF1/RBP-Jκ is converted from a repressor to an activator of gene transcription. Similarly, the Epstein Barr viral oncoprotein EBNA2, which is required for B-cell immortalization, activates genes through CBF1. Moreover, the TAN-1 and int-3 oncogenes represent activated versions of Notch1 and Notch4, respectively. Here, we show that the adenoviral oncoprotein 13S E1A also binds to CBF1/RBP-Jκ, displaces associated corepressor complexes, and activates CBF1/RBP-Jκ-dependent gene expression. Our results suggest that the central role of the Notch-CBF1/RBP-Jκ signaling pathway in cell fate decisions renders it susceptible to pathways of viral replication and oncogenic conversion.