近日，以京都大学医学研究科教授长田重一为首的研究人员证实，对动物身体正常发育不可或缺的基因EYA还具有新功能：即能够促使细胞制造出攻击病毒的蛋白质——干扰素。该研究成果发表在最近出版的《自然》杂志电子版上。
EYA(eyes absent)是一个在进化上非常保守的基因家族，EYA蛋白作为重要的转录调控因子，直接参与胚胎发育过程中的细胞增殖、组织分化和器官发育。此次研究人员使用大鼠细胞进行试验，探索与免疫有关的基因活动。在试验中研究人员发现，由EYA产生的蛋白质与担当“传感器”探知病毒感染的分子关系十分密切，二者一会儿紧贴在一起，一会儿离开。以此为契机继续研究，结果发现当EYA基因活动增强时，细胞就会大量合成能够攻击病毒的干扰素。
研究人员称，这项研究成果对今后判明免疫系统疾病以及遗传病的病理具有积极意义。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 28 June 2009 | doi:10.1038/nature08138
Regulation of the innate immune response by threonine-phosphatase of Eyes absent
Yasutaka Okabe1,2,3,4, Teruyuki Sano1,4 & Shigekazu Nagata1,2
1 Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan
2 Solution Oriented Research for Science and Technology, and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kyoto 606-8501, Japan
Innate immunity is stimulated not only by viral or bacterial components, but also by non-microbial danger signals (damage-associated molecular patterns)1. One of the damage-associated molecular patterns is chromosomal DNA that escapes degradation. In programmed cell death and erythropoiesis, DNA from dead cells or nuclei expelled from erythroblasts is digested by DNase II in the macrophages after they are engulfed. DNase II-/- (also known as Dnase2a-/-) mice suffer from severe anaemia or chronic arthritis due to interferon- (IFN-) and tumour necrosis factor- (TNF-) produced from the macrophages carrying undigested DNA2, 3 in a Toll-like receptor (TLR)-independent mechanism4. Here we show that Eyes absent 4 (EYA4), originally identified as a co-transcription factor, stimulates the expression of IFN- and CXCL10 in response to the undigested DNA of apoptotic cells. EYA4 enhanced the innate immune response against viruses (Newcastle disease virus and vesicular stomatitis virus), and could associate with signalling molecules (IPS-1 (also known as MAVS), STING (TMEM173) and NLRX1). Three groups have previously shown that EYA has phosphatase activity5, 6, 7. We found that mouse EYA family members act as a phosphatase for both phosphotyrosine and phosphothreonine. The haloacid dehalogenase domain at the carboxy terminus contained the tyrosine-phosphatase, and the amino-terminal half carried the threonine-phosphatase. Mutations of the threonine-phosphatase, but not the tyrosine-phosphatase, abolished the ability of EYA4 to enhance the innate immune response, suggesting that EYA regulates the innate immune response by modulating the phosphorylation state of signal transducers for the intracellular pathogens.
