A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the embryo. Author Maira Cardoso, Marcio Fontenele, Bomyi Lim, Paulo Bisch, Stanislav Shvartsman, Helena Araujo Publication Year 2017 Type Journal Article Abstract The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the embryo, Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IκB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFκB effector Dorsal. Here, we investigate how modulates Toll signals through its effects on the Dorsal gradient and on Dorsal target genes. Quantitative analysis using a series of loss- and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient can behave differently with respect to Cactus fluctuations. In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from the mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as a NFκB inhibitor, ensuring a correct response to Toll signals. Keywords Animals, Drosophila, Drosophila Proteins, Nuclear Proteins, Transcription Factors, Phosphoproteins, DNA-Binding Proteins, Embryo, Nonmammalian, Alleles, Calpain Journal Development Volume 144 Issue 16 Pages 2907-2913 Date Published 2017 Aug 15 ISSN Number 1477-9129 DOI 10.1242/dev.145557 Alternate Journal Development PMCID PMC5592809 PMID 28705899 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML