SUMOylation of Dorsal attenuates Toll/NF-κB signaling.

IF 3.3 3区 生物学
Genetics Pub Date : 2022-07-04 DOI:10.1093/genetics/iyac081
Sushmitha Hegde, Ashley Sreejan, Chetan J Gadgil, Girish S Ratnaparkhi
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引用次数: 0

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.

背侧sumo化可减弱Toll/NF-κB信号
在果蝇中,Toll/NF-κB信号在动物发育和宿主防御中都起着关键作用。Toll信号的激活、强度和动力学受Toll/NF-κB级联中多种蛋白的磷酸化、sumo化或泛素化等翻译后修饰调控。在这里,我们已经生成了CRISPR-Cas9编辑的具有SUMO偶联抗性(SCR)的Dorsal (DL)变体。有趣的是,dlSCR母亲产下的胚胎克服了dl单倍体不足并完成了发育程序。这种能力似乎是DLSCR更高转录激活的结果。相反,SUMOylation抑制DL转录激活,最终赋予背-腹侧程序稳健性。在幼虫免疫应答中,dlSCR动物表现出晶体细胞数量增加、体液防御基因激活增强、高仙人掌水平和DL: cactus复合物细胞质稳定。一个数学模型评估了一小部分SUMO化DL(<5%)的贡献,表明它可以阻断转录激活,主要由非SUMO共轭的DL驱动。我们的研究结果将SUMO偶联定义为Toll信号级联的重要调节因子,在发育和宿主防御中都是如此。我们的研究结果广泛表明,SUMO在转录激活水平上减弱DL。此外,我们假设DL的SUMO共轭可能是抑制Toll/NF-κB信号传导的Ubc9依赖反馈电路的一部分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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