Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi, 464-8602, Japan.
Genes Cells. 2013 Nov;18(11):934-45. doi: 10.1111/gtc.12085. Epub 2013 Aug 6.
The IMD pathway is one of the major regulators of the innate immune response in Drosophila. Although extensive analysis of the IMD pathway has been carried out, precise mechanisms for how each target gene of the pathway is down-regulated remain to be clarified. Here, we carried out genetic screening and found that fat facets (faf), which encodes a deubiquitinating enzyme, inhibited the expression of the target genes of the IMD pathway. Overexpression of faf suppressed the infection-induced expression of Diptericin and increased susceptibility to bacterial infection in flies, whereas faf loss-of-function mutants decreased susceptibility. Time course analysis revealed that specific subsets of the target genes of the IMD pathway were affected by faf. Biochemical analysis showed that Faf made a complex with Imd, and both Faf and Imd were polyubiquitinated when they were co-overexpressed. Given that faf-dependent Imd polyubiquitination did not seem to cause protein degradation of Imd, Faf might inhibit the IMD pathway by modulating the state of Imd ubiquitination and/or stability.
IMD 途径是果蝇固有免疫反应的主要调节者之一。尽管对 IMD 途径进行了广泛的分析，但途径中每个靶基因的下调的确切机制仍有待阐明。在这里，我们进行了遗传筛选，发现编码去泛素化酶的 fat facets (faf) 抑制了 IMD 途径的靶基因的表达。faf 的过表达抑制了 Diptericin 的感染诱导表达，并增加了果蝇对细菌感染的易感性，而 faf 功能丧失突变体则降低了易感性。时程分析显示，faf 影响 IMD 途径的特定靶基因亚群。生化分析表明 Faf 与 Imd 形成复合物，当它们共过表达时，Faf 和 Imd 都被多泛素化。鉴于 faf 依赖的 Imd 多泛素化似乎不会导致 Imd 的蛋白降解，Faf 可能通过调节 Imd 的泛素化和/或稳定性来抑制 IMD 途径。
