Neoplastic transformation by Notch is independent of transcriptional activation by RBP-J signalling

Signalling through the transmembrane receptor Notch is triggered by ligand binding, which induces the proteolytic cleavage of the Notch protein. This cleavage generates an intracellular fragment of the Notch protein (Notch-IC ), which translocates into the nucleus and modifies transcription of target genes through its association with the RBP-J protein, Thus, the isolated N otch-IC protein represents the constitutively activated receptor. We have p erformed a deletion analysis of Notch IC in order to identify the transfera ble transactivation domain of Notch-IC and the minimal domain of Notch-TC r equired for RBP-J dependent transactivational activation. Functionally, Not ch-IC has been Linked to cell fate decision in development and oncogenesis in vivo. In vitro, Notch-IC can cooperate in neoplastic transformation of b aby rat kidney cells with the adenoviral E1A protein. We have defined the m inimal domain of Notch-IC required for E1A cotransformation. This domain, c onsisting of the ankyrin repeats of Notch-IC only, can neither activate RBP -J dependent transcription nor does it carry a transactivation domain. Ther efore, the ankyrin repeat domain of Notch-IC might trigger novel pathways r elevant for transformation but unrelated to RBP-J signalling.