The Drosophila Notch (N) gene encodes a conserved single-pass transmem
brane receptor that transduces extracellular signals controlling cell
fate. Here, we present evidence that the intracellular domain of Notch
gains access to the nucleus in response to ligand, possibly through a
mechanism involving proteolytic cleavage and release from the remaind
er of the protein. In addition, our results suggest that signal transd
uction by Notch depends on the ability of the intracellular domain, pa
rticularly the portion containing the CDC10 repeats, to reach the nucl
eus and to participate in the transcriptional activation of downstream
target genes.