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

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.