@article{3132, keywords = {Animals, Drosophila, Drosophila Proteins, Nuclear Proteins, Transcription Factors, Phosphoproteins, DNA-Binding Proteins, Embryo, Nonmammalian, Alleles, Calpain}, author = {Maira Cardoso and Marcio Fontenele and Bomyi Lim and Paulo Bisch and Stanislav Shvartsman and Helena Araujo}, title = {A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the embryo.}, 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.

}, year = {2017}, journal = {Development}, volume = {144}, pages = {2907-2913}, month = {2017 Aug 15}, issn = {1477-9129}, doi = {10.1242/dev.145557}, language = {eng}, }