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Signalling downstream of activated mammalian Notch

Abstract

NOTCH belongs to a family of transmembrane proteins that are widely conserved from flies to vertebrates and are thought to be involved in cell-fate decisions. In Drosophila, the Suppressor of hairless (Su(H)) gene1,2 and genes of the Enhancer of split (E(Spl)) complex, which encode proteins of the basic helix–loop–helix type3,4 have been implicated in the Notch signalling pathway. Mammalian homologues of E(Spl), such as the mouse Hairy enhancer of split (HES-1 )5, have been isolated. Both HES-1 and the intracellular domain of murine Notch (mNotch) are able to block MyoD-induced myogenesis5-7. Here we show that activated forms of mNotch associate with the human analogue of Su(H), KBF2/RBP-JK (refs 8, 9) and act as transcriptional activators through the KBF2-binding sites of the HES-1 promoter.

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