病毒有很多詭計用于躲避免疫系統(tǒng),。在2009年9月7日的Journal of Cell Biology雜志上,，Stagg等人揭示了其中的一個病毒詭計的關(guān)鍵細(xì)節(jié)。該病毒會識別一種蛋白,，而這種蛋白使得巨細(xì)胞病毒能夠關(guān)閉機(jī)體對其的防御,。
巨細(xì)胞病毒（Cytomegalovirus）能夠通過靶向定位MHC I蛋白躲避免疫系統(tǒng)的監(jiān)視。當(dāng)機(jī)體受到感染時,，MHC I會捕獲少量的病毒蛋白,，并將其呈現(xiàn)到病毒素T細(xì)胞，從而殺死細(xì)胞停住繼續(xù)感染,。然而兩個巨細(xì)胞病毒基因會欺騙細(xì)胞泛激素化MHC I 并在蛋白酶體中將其摧毀,。為了引起MHC I泛激素化，基因會選擇一個叫E3連接酶的蛋白,。研究人員解釋說,，目前，還不是很清楚這個蛋白的身份,。
使用RNA干擾技術(shù),，Stagg篩選了373種候選物，發(fā)現(xiàn)一種叫TRC8的連接酶可以保護(hù)MHC I,。TRC8的突變體能夠截斷泛激素化使得MHC I恢復(fù)功能,。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Cell Biology doi:10.1083/jcb.200906110
The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER
Helen R. Stagg1, Mair Thomas1, Dick van den Boomen1, Emmanuel J.H.J. Wiertz2, Harry A. Drabkin3, Robert M. Gemmill3, and Paul J. Lehner1
1 Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, England, UK
2 University Medical Centre Utrecht, 3584 CX Utrecht, Netherlands
3 Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
The US2 and US11 gene products of human cytomegalovirus promote viral evasion by hijacking the endoplasmic reticulum (ER)–associated degradation (ERAD) pathway. US2 and US11 initiate dislocation of newly translocated major histocompatibility complex class I (MHC I) from the ER to the cytosol for proteasome-mediated degradation, thereby decreasing cell surface MHC I. Despite being instrumental in elucidating the mammalian ERAD pathway, the responsible E3 ligase or ligases remain unknown. Using a functional small interfering RNA library screen, we now identify TRC8 (translocation in renal carcinoma, chromosome 8 gene), an ER-resident E3 ligase previously implicated as a hereditary kidney cancer gene, as required for US2-mediated MHC I ubiquitination. Depletion of TRC8 prevents MHC I ubiquitination and dislocation by US2 and restores cell surface MHC I. TRC8 forms an integral part of a novel multiprotein ER complex that contains MHC I, US2, and signal peptide peptidase. Our data show that the TRC8 E3 ligase is required for MHC I dislocation from the ER and identify a new complex associated with mammalian ERAD.
