Yagi Yoshimasa, Ip Y Tony
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
EMBO Rep. 2005 Nov;6(11):1088-94. doi: 10.1038/sj.embor.7400542. Epub 2005 Sep 30.
We have identified a novel component, Helicase89B, that is required for the inducible antimicrobial response in Drosophila larvae by means of a P-element insertional genetic screen. Helicase89B belongs to the Mot1p/BTAF1 subfamily of SNF2-like ATPases. This subfamily can interact with TATA-binding proteins, but whether the interaction leads to gene activation or repression is being debated. We found that Helicase89B is required for the inducible expression of antimicrobial peptide genes but not for the inducible expression of heat-shock genes. The antimicrobial peptide genes are activated by the Toll and immune deficiency (IMD) signalling pathways. Genetic experiments show that Helicase89B acts downstream of DIF and Relish, the two nuclear factor-kappaB (NF-kappaB)-related transcription factors that mediate Toll- and IMD-stimulated antimicrobial response. Thus, Helicase89B positively regulates gene expression during innate immune response and may act as a link between NF-kappaB-related transcription factors and the basal transcription machinery.
我们通过P因子插入遗传筛选,鉴定出一种新的成分——解旋酶89B,它是果蝇幼虫诱导性抗菌反应所必需的。解旋酶89B属于SNF2样ATP酶的Mot1p/BTAF1亚家族。该亚家族可与TATA结合蛋白相互作用,但这种相互作用导致基因激活还是抑制仍存在争议。我们发现,抗菌肽基因的诱导性表达需要解旋酶89B,但热休克基因的诱导性表达则不需要。抗菌肽基因由Toll和免疫缺陷(IMD)信号通路激活。遗传学实验表明,解旋酶89B在DIF和Relish下游起作用,DIF和Relish是两种与核因子κB(NF-κB)相关的转录因子,介导Toll和IMD刺激的抗菌反应。因此,解旋酶89B在先天免疫反应中正向调节基因表达,可能作为NF-κB相关转录因子与基础转录机制之间的联系。