S. Kidd et al., Ligand-induced cleavage and regulation of nuclear entry of Notch in Drosophila melanogaster embryos, GENE DEV, 12(23), 1998, pp. 3728-3740
Notch, a transmembrane protein found in a wide range of organisms, is a com
ponent of a pathway that mediates cell-fate decisions that involve intercel
lular communication. In this paper, we show that in Drosophila melanogaster
, Notch (N) is processed in a ligand-dependent fashion to generate phosphor
ylated, soluble intracellular derivatives. Suppressor of Hairless [Su(H)] i
s predominantly associated with soluble intracellular N. It has been demons
trated by others that N has access to the nucleus, and we show that when te
thered directly to DNA, the cytoplasmic domain of N can activate transcript
ion. Conversely, a viral activator fused to Su(H) can substitute for at lea
st some N functions during embryogenesis. We suggest that one function of s
oluble forms of N is to bind to Su(H), and in the nucleus, to act directly
as a transcriptional transactivator of the latter protein. Although N has f
unctional nuclear localization signals, the N/Su(H) complex accumulates in
the cytoplasm and on membranes suggesting that its nuclear entry is regulat
ed. Localization studies in cultured cells and embryos suggest that Su(H) p
lays a role in this regulation, with the relative levels of Delta, N and Su
(H) determining whether a N/Su(H) complex enters the nucleus.