@article {Cardoso079814, author = {Maira Arruda Cardoso and Marcio Fontenele and Bomyi Lim and Paulo Mascarello Bisch and Stanislav Shvartsman and Helena Marcolla Araujo}, title = {A Novel function for Cactus/IκB inhibitor to promote Toll signals in the Drosophila embryo}, elocation-id = {079814}, year = {2016}, doi = {10.1101/079814}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila 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 nuclear gradient of the NFκB effector Dorsal. Here we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and 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 behave differently respective to Cactus fluctuations. Unexpectedly, Cactus favors Dorsal nuclear localization required as response to high Toll signals at the ventral side of the embryo. Furthermore, N-terminal deleted Cactus mimics these effects, indicating that the ability of Cactus to favor Toll stems from mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that unexplored mechanisms are at play to ensure a correct response to high Toll signals.Summary: The IκB protein Cactus favors high Toll signals, revealing that the ventral and lateral aspects of the Dorsal/NFκB nuclear gradient behave differently respective to Cactus concentrations in the Drosophila embryo.}, URL = {https://www.biorxiv.org/content/early/2016/10/07/079814}, eprint = {https://www.biorxiv.org/content/early/2016/10/07/079814.full.pdf}, journal = {bioRxiv} }