Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity
Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity
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DOI：
10.1073/pnas.100391597
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发表时间：
2000-05-23
影响因子：
11.1
通讯作者：
Kimbrell, DA
中科院分区：
文献类型：
--
作者：
Bernal, A;Kimbrell, DA
Thou基因已被鉴定为一种参与果蝇宿主免疫防御的新型基因。Thor是4 E结合蛋白（4 E-BP）家族的成员，其在哺乳动物中已被定义为通过结合真核起始因子4 E（eIF 4 E）控制翻译起始的途径中的关键调节剂。在没有感染的情况下，Thor在所有发育阶段中表达，并且转录本定位于多种组织，包括生殖系统。为了应对细菌感染，以及较小程度上的受伤，Thor会上调。Thor启动子具有典型的NF κ B和相关的加塔识别序列，这些序列已被证明是免疫诱导所必需的，以及果蝇免疫应答基因中常见的其他序列，包括干扰素相关的调节序列。在存活测试中，Thor突变体显示出免疫受损的症状，表明Thor可能在宿主防御中至关重要。与Thor相反，果蝇eIF 4 E不受细菌感染诱导。Thor的这些发现提供了第一个证据，证明4 E-BP家族成员在任何生物体的免疫诱导中发挥作用。此外，先前没有发现包括4 E-BP的翻译起始途径中的基因是免疫诱导的。我们的研究结果表明，无论是在体液免疫或一个新的，非翻译功能的4 E-BP型基因的翻译调节的作用。
Thou has been identified as a new type of gene involved in Drosophila host immune defense. Thor is a member of the 4E-binding protein (4E-BP) family, which in mammals has been defined as critical regulators in a pathway that controls initiation of translation through binding eukaryotic initiation factor 4E (eIF4E), Without an infection, Thor is expressed during all developmental stages and transcripts localize to a wide variety of tissues, including the reproductive system. In response to bacterial infection and, to a lesser extent, by wounding, Thor is up-regulated. The Thor promoter has the canonical NF kappa B and associated GATA recognition sequences that have been shown to be essential for immune induction, as well as other sequences commonly found for Drosophila immune response genes, including interferon-related regulatory sequences, In survival tests, Thor mutants show symptoms of being immune compromised, indicating that Thor may be critical in host defense. In contrast to Thor, Drosophila eIF4E is not induced by bacterial infection. These findings for Thor provide the first evidence that a 4E-BP family member has a role in immune induction in any organism. Further, no gene in the translation initiation pathway that includes 4E-BP has been previously found to be immune induced. Our results suggest either a role for translational regulation in humoral immunity or a new, nontranslational function for 4E-BP type genes.