SIGNALING DOWNSTREAM OF ACTIVATED MAMMALIAN NOTCH

NOTCH belongs to a family of transmembrane proteins that are widely co nserved from flies to vertebrates and are thought to be involved in ce ll-fate decisions. In Drosophila, the Suppressor of hairless (Su(H)) g ene(1,2) and genes of the Enhancer of split (E(Spl)) complex, which en code proteins of the basic helix-loop-helix type(3,4) have been implic ated in the Notch signalling pathway. Mammalian homologues of E(Spl), such as the mouse Hairy enhancer of split (HES-1)(5), have been isolat ed. Both HES-1 and the intracellular domain of murine Notch (mNotch) a re able to block MyoD-induced myogenesis(5-7). Here we show that activ ated forms of mNotch associate with the human analogue of Su(H), KBF2/ RBP-J kappa (refs 8,9) and act as transcriptional activators through t he KBF2-binding sites of the HES-1 promoter.