澳大利亞昆士蘭大學分子生物科學系,，放射生物學與腫瘤學實驗室的研究者研究Caspase活性獲得新突破，最新成果結論發(fā)表在1月份的Science雜志上,。
Caspases是近年來發(fā)現(xiàn)的一組存在于胞質溶膠中的結構上相關的半胱氨酸蛋白酶，它們的一個重要共同點是特異地斷開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,，這種切割只發(fā)生在少數(shù)（通常只有1個）位點上,，主要是在結構域間的位點上，切割的結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。
外源性的核酸能激活哺乳動物的天然免疫應答反應,。一旦探測到細胞質中存在有外源性的雙鏈DNA（double stranded DNA）,，免疫系統(tǒng)就會開始工作激起特異性的抗病毒應答和巨噬細胞死亡活動。細胞質里的雙鏈DNA能快速激活骨髓衍生的巨噬細胞中的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的結合蛋白,，能穩(wěn)定并快速地轉染DNA。研究者敲除p202表達基因,，研究p202的功能,，結果發(fā)現(xiàn)p202是DNA誘導Caspase激活反應的抑制因子。而相反的是,，HIN200因子和AIM2（p210）是細胞質激活Caspase的激動劑,。這些研究結果表明，HIN-200蛋白家族是細胞質外源雙鏈DNA介導的Caspase活化反應的識別啟動因子,。（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.
