近日,，以京都大學(xué)醫(yī)學(xué)研究科教授長(zhǎng)田重一為首的研究人員證實(shí),，對(duì)動(dòng)物身體正常發(fā)育不可或缺的基因EYA還具有新功能：即能夠促使細(xì)胞制造出攻擊病毒的蛋白質(zhì)——干擾素。該研究成果發(fā)表在最近出版的《自然》雜志電子版上,。
EYA(eyes absent)是一個(gè)在進(jìn)化上非常保守的基因家族,，EYA蛋白作為重要的轉(zhuǎn)錄調(diào)控因子，直接參與胚胎發(fā)育過(guò)程中的細(xì)胞增殖,、組織分化和器官發(fā)育,。此次研究人員使用大鼠細(xì)胞進(jìn)行試驗(yàn)，探索與免疫有關(guān)的基因活動(dòng),。在試驗(yàn)中研究人員發(fā)現(xiàn),，由EYA產(chǎn)生的蛋白質(zhì)與擔(dān)當(dāng)“傳感器”探知病毒感染的分子關(guān)系十分密切，二者一會(huì)兒緊貼在一起,，一會(huì)兒離開,。以此為契機(jī)繼續(xù)研究,，結(jié)果發(fā)現(xiàn)當(dāng)EYA基因活動(dòng)增強(qiáng)時(shí),，細(xì)胞就會(huì)大量合成能夠攻擊病毒的干擾素。
研究人員稱,，這項(xiàng)研究成果對(duì)今后判明免疫系統(tǒng)疾病以及遺傳病的病理具有積極意義,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
