02217nas a2200229   4500008004100000022001400041245006300055210006100118260000900179490000800188520152000196653001501716653002301731653002001754653000901774653001801783100002101801700002001822700002301842700002801865856009401893       2022                        eng d  a0016-673100aSUMOylation of dorsal attenuates Toll/NF-kappa B signaling0 aSUMOylation of dorsal attenuates TollNFkappa B signaling  cJUL 0 v2213 a<p>
	In Drosophila, Toll/NF-kappa B 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-kappa B cascade. Here, we have generated a CRISPR-Cas9 edited Dorsal (DL) variant that is SUMO conjugation resistant. Intriguingly, embryos laid by dl(SCR) 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, dl(SCR) 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-kappa B signaling.</p>
10aDrosophila10ahaploinsufficiency10ainnate immunity10aSUMO10atranscription1 aHegde, Sushmitha1 aSreejan, Ashley1 aGadgil, Chetan, J.1 aRatnaparkhi, Girish, S.  uhttps://library.ncl.res.in/content/sumoylation-dorsal-attenuates-tollnf-kappa-b-signaling