CACTUS PROTEIN-DEGRADATION MEDIATES DROSOPHILA DORSAL-VENTRAL SIGNALING

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.