
<ArticleTitle>Separable and redundant regulatory determinants in <prot>Cactus</prot> mediate its dorsal group dependent degradation.</ArticleTitle>
<AbstractText>Dorsal-ventral polarity within the Drosophila syncytial blastoderm embryo is determined by the maternally encoded dorsal group signal transduction pathway that regulates nuclear localization of the transcription factor <prot>Dorsal</prot>. Nuclear uptake of <prot>Dorsal</prot>, a <prot>Rel</prot>/<prot>NFkappaB</prot> homolog, is controlled by the interaction with its cognate <prot>IkappaB</prot> inhibitor protein <prot>Cactus</prot>, which is degraded on the ventral side of the embryo in response to dorsal group signaling. Previous studies have suggested that an N-terminally located kinase target motif similar to that found in <prot>IkappaB</prot> proteins is involved in the spatially controlled degradation of <prot>Cactus</prot>. We report studies of the in vivo function and distribution of fusion proteins comprising segments of <prot>Cactus</prot> attached to Escherichia coli <prot>beta-galactosidase</prot> (<prot>lacZ</prot>). Full-length <prot>Cactus</prot>-<prot>lacZ</prot> expressed in vivo normalizes the ventralized phenotype of embryos that lack <prot>Cactus</prot> and faithfully reconstitutes dorsal group-regulated degradation, while fusion protein constructs that lack the first 125 amino acids of <prot>Cactus</prot> escape dorsal group-dependent degradation. Furthermore, <prot>Cactus</prot>-<prot>lacZ</prot> constructs that lack only the putative <prot>IkappaB</prot>-dependent kinase target-like motif can nevertheless undergo spatially regulated dorsal group-dependent degradation and we have identified the regulatory determinant responsible for dorsal group-dependent degradation of <prot>Cactus</prot> in the absence of this motif. Taken together, our studies indicate the presence of two distinct redundantly acting determinants in the N terminus of <prot>Cactus</prot> that direct dorsal group-dependent degradation. Strikingly, the regulatory domain of human <prot>IkappaBalpha</prot> can also direct polarized degradation of <prot>Cactus</prot>-<prot>lacZ</prot> fusion protein.</AbstractText>
