SUMOylation of Dorsal attenuates Toll/NF-kB signaling.
In Drosophila, Toll/NF-jB 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...
| Publicado en: | Genetics Vol. 221; no. 3; pp. 1 - 21 |
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| Autores principales: | , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Jul2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=158070735&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 158070735 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00166731 GNT jtl: Genetics issn: 00166731 maglogo: N pubinfo: dt: Jul2022 vid: 221 iid: 3 pid: 622 pub: Oxford University Press / USA artinfo: ui: 158070735 158070735 158070735 10.1093/genetics/iyac081 158070735 ppf: 1 ppct: 20 formats: tig: atl: SUMOylation of Dorsal attenuates Toll/NF-kB signaling. aug: au: Hegde, Sushmitha Sreejan, Ashley Gadgil, Chetan J. Ratnaparkhi, Girish S. affil: Biology, Indian Institute of Science Education & Research, Pune 411008, India sug: subj: Proteins Metabolism Signal Transduction NF-kappa B Metabolism Insects Phosphorylation Models, Statistical CRISPR-Associated Proteins Metabolism Immunity Descriptive Statistics Genetic Variation Transcription Factors Metabolism ab: In Drosophila, Toll/NF-jB 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-jB 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-jB signaling. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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