In a genetic screen for mutations that attenuate Notch signaling in th
e developing Drosophila eye, we isolated rare, gain-of-function allele
s of Suppressor of Hairless (Su(H)), the fly homolog of the mammalian
C promoter-binding factor 1 (CBF1) gene. Su(H) exhibits numerous allel
e-specific genetic interactions with Notch as well as with Delta, delt
ex, and mastermind. In cultured Drosophila cells, the Su(H) protein is
sequestered in the cytoplasm when coexpressed with Notch protein and
is translocated to the nucleus when Notch binds to its ligand Delta. C
ytoplasmic retention of Su(H) requires the intracellular cdc10/ankyrin
repeats of Notch, which associate with SU(H) protein in the yeast int
eraction trap assay. These results indicate that Notch activity may re
gulate nuclear events by controlling the activity of a DNA-binding pro
tein.