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SUMOylation of Dorsal attenuates Toll/NF-κB signaling

Show simple item record HEGDE, SUSHMITHA en_US Sreejan, Ashley en_US Gadgil, Chetan J. en_US RATNAPARKHI, GIRISH S. en_US 2022-06-16T04:23:35Z 2022-06-16T04:23:35Z 2022-07 en_US
dc.identifier.citation Genetics, 221(3). en_US
dc.identifier.issn 0016-6731 en_US
dc.identifier.issn 1943-2631 en_US
dc.identifier.uri en_US
dc.description.abstract In Drosophila, Toll/NF-κB signaling plays key roles in both animal development and in host defense. The activation, intensity, and kinetics of Toll signaling are regulated by posttranslational modifications such as phosphorylation, SUMOylation, or ubiquitination that target multiple proteins in the Toll/NF-κB cascade. Here, we have generated a CRISPR-Cas9 edited Dorsal (DL) variant that is SUMO conjugation resistant. Intriguingly, embryos laid by dlSCR mothers overcome dl haploinsufficiency and complete the developmental program. This ability appears to be a result of higher transcriptional activation by DLSCR. In contrast, SUMOylation dampens DL transcriptional activation, ultimately conferring robustness to the dorso-ventral program. In the larval immune response, dlSCR animals show an increase in crystal cell numbers, stronger activation of humoral defense genes, and high cactus levels. A mathematical model that evaluates the contribution of the small fraction of SUMOylated DL (1–5%) suggests that it acts to block transcriptional activation, which is driven primarily by DL that is not SUMO conjugated. Our findings define SUMO conjugation as an important regulator of the Toll signaling cascade, in both development and host defense. Our results broadly suggest that SUMO attenuates DL at the level of transcriptional activation. Furthermore, we hypothesize that SUMO conjugation of DL may be part of a Ubc9-dependent mechanism that restrains Toll/NF-κB signaling. en_US
dc.language.iso en en_US
dc.publisher Oxford University Press en_US
dc.subject Drosophila en_US
dc.subject Haploinsufficiency|Innate immunity en_US
dc.subject SUMO en_US
dc.subject transcription en_US
dc.subject 2022-JUN-WEEK3 en_US
dc.subject TOC-JUN-2022 en_US
dc.subject 2022 en_US
dc.title SUMOylation of Dorsal attenuates Toll/NF-κB signaling en_US
dc.type Article en_US
dc.contributor.department Dept. of Biology en_US
dc.identifier.sourcetitle Genetics en_US
dc.publication.originofpublisher Foreign en_US

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