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A Novel function for Cactus/IκB inhibitor to promote Toll signals in the Drosophila embryo

Maira Arruda Cardoso, Marcio Fontenele, Bomyi Lim, Paulo Mascarello Bisch, Stanislav Shvartsman, Helena Marcolla Araujo
doi: https://doi.org/10.1101/079814
Maira Arruda Cardoso
1Instituto de Ciências Biomédicas, Federal University of Rio de Janeiro
4Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro
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Marcio Fontenele
1Instituto de Ciências Biomédicas, Federal University of Rio de Janeiro
2Institute of Molecular Entomology
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Bomyi Lim
3Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ
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Paulo Mascarello Bisch
4Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro
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Stanislav Shvartsman
3Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ
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Helena Marcolla Araujo
1Instituto de Ciências Biomédicas, Federal University of Rio de Janeiro
2Institute of Molecular Entomology
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 07, 2016.
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A Novel function for Cactus/IκB inhibitor to promote Toll signals in the Drosophila embryo
Maira Arruda Cardoso, Marcio Fontenele, Bomyi Lim, Paulo Mascarello Bisch, Stanislav Shvartsman, Helena Marcolla Araujo
bioRxiv 079814; doi: https://doi.org/10.1101/079814
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A Novel function for Cactus/IκB inhibitor to promote Toll signals in the Drosophila embryo
Maira Arruda Cardoso, Marcio Fontenele, Bomyi Lim, Paulo Mascarello Bisch, Stanislav Shvartsman, Helena Marcolla Araujo
bioRxiv 079814; doi: https://doi.org/10.1101/079814

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