澳大利亞昆士蘭大學(xué)分子生物科學(xué)系,，放射生物學(xué)與腫瘤學(xué)實(shí)驗(yàn)室的研究者研究Caspase活性獲得新突破,，最新成果結(jié)論發(fā)表在1月份的Science雜志上。
Caspases是近年來發(fā)現(xiàn)的一組存在于胞質(zhì)溶膠中的結(jié)構(gòu)上相關(guān)的半胱氨酸蛋白酶,，它們的一個(gè)重要共同點(diǎn)是特異地?cái)嚅_天冬氨酸殘基后的肽鍵,。Caspase能夠高度選擇性地切割某些蛋白質(zhì)，這種切割只發(fā)生在少數(shù)（通常只有1個(gè)）位點(diǎn)上,，主要是在結(jié)構(gòu)域間的位點(diǎn)上,，切割的結(jié)果或是活化某種蛋白，或使某種蛋白失活,，但從不完全降解一種蛋白質(zhì),。
外源性的核酸能激活哺乳動(dòng)物的天然免疫應(yīng)答反應(yīng)。一旦探測到細(xì)胞質(zhì)中存在有外源性的雙鏈DNA（double stranded DNA）,，免疫系統(tǒng)就會(huì)開始工作激起特異性的抗病毒應(yīng)答和巨噬細(xì)胞死亡活動(dòng),。細(xì)胞質(zhì)里的雙鏈DNA能快速激活骨髓衍生的巨噬細(xì)胞中的Caspase3和Caspase1酶。
在本研究中,，研究人員發(fā)現(xiàn)HIN-200家族成員和lupus susceptibility factor,，p202是雙鏈DNA的結(jié)合蛋白,，能穩(wěn)定并快速地轉(zhuǎn)染DNA。研究者敲除p202表達(dá)基因,，研究p202的功能,，結(jié)果發(fā)現(xiàn)p202是DNA誘導(dǎo)Caspase激活反應(yīng)的抑制因子。而相反的是,，HIN200因子和AIM2（p210）是細(xì)胞質(zhì)激活Caspase的激動(dòng)劑,。這些研究結(jié)果表明，HIN-200蛋白家族是細(xì)胞質(zhì)外源雙鏈DNA介導(dǎo)的Caspase活化反應(yīng)的識(shí)別啟動(dòng)因子,。（生物谷Bioon.com）
生物谷推薦原始出處：
Science Published Online January 8, 2009 Science DOI: 10.1126/science.1169841
HIN-200 Proteins Regulate Caspase Activation in Response to Foreign Cytoplasmic DNA
Tara L. Roberts 1, Adi Idris 2, Jasmyn A. Dunn 2, Greg M. Kelly 2, Carol M. Burnton 2, Samantha Hodgson 2, Lani L. Hardy 2, Valerie Garceau 3, Matthew J. Sweet 4, Ian L. Ross 2, David A. Hume 3, Katryn J. Stacey 4*
1 The University of Queensland, Institute for Molecular Bioscience, Qld 4072, Australia.; Present address: Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia.
2 The University of Queensland, Institute for Molecular Bioscience, Qld 4072, Australia.
3 The University of Queensland, Institute for Molecular Bioscience, Qld 4072, Australia.; Present Address: The Roslin Institute, University of Edinburgh, Roslin EH259PS, Scotland, UK.
4 The University of Queensland, School of Chemistry and Biomolecular Science, Qld 4072, Australia.
The mammalian innate immune system is activated by foreign nucleic acids. Detection of double-stranded DNA (dsDNA) in the cytoplasm triggers characteristic antiviral responses and macrophage cell death. Cytoplasmic dsDNA rapidly activated caspase 3 and caspase 1 in bone marrow-derived macrophages. We identified the HIN-200 family member and lupus susceptibility factor, p202, as a dsDNA binding protein that bound stably and rapidly to transfected DNA. Knockdown studies identified p202 as an inhibitor of DNA-induced caspase activation. Conversely, the related pyrin domain-containing HIN-200 factor, AIM2 (p210), was required for caspase activation by cytoplasmic dsDNA. This work indicates that HIN-200 proteins can act as pattern recognition receptors mediating responses to cytoplasmic dsDNA.
