Dorsal-ventral patterning in the Drosophila embryo relies on a signal
transduction pathway that is similar to a signaling pathway leading to
the activation of the mammalian transcription factor NF-kappa B. Stim
ulation of this Drosophila pathway on the ventral side of the embryo c
auses the nuclear translocation of Dorsal, the Drosophila NF-kappa B h
omolog. Cactus, like its mammalian homolog I kappa B, inhibits nuclear
translocation by binding Dorsal and retaining it in the cytoplasm. We
show that Cactus, like I kappa B, is rapidly degraded in response to
signaling. More importantly, signal-dependent degradation of Cactus do
es not require the presence of Dorsal, indicating that Cactus degradat
ion is a direct response to signaling, and that disruption of the Dors
al/Cactus complex is a secondary result of Cactus degradation. Mutant
alleles of cactus that encode more stable forms of the protein block s
ignaling, showing that efficient degradation is necessary for signalin
g. We find that Cactus protein stability is regulated by two independe
nt processes that rely on different regions within the protein: signal
-dependent degradation requires sequences in the amino terminus or ank
yrin repeats, whereas signal-independent degradation of free Cactus re
quires the carboxy-terminal region of the protein that includes a PEST
sequence.