Yin Yili, Manoury Bénédicte, Fåhraeus Robin
Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Science. 2003 Sep 5;301(5638):1371-4. doi: 10.1126/science.1088902.
The glycine-alanine repeat domain (GAr) of Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1) prevents major histocompatibility complex (MHC) class I-restricted presentation of EBNA1 epitopes to cytotoxic T cells. This effect has previously been attributed to the ability of GAr to inhibit its own proteasomal degradation. Here we show, both in vitro and in vivo, that GAr also inhibits messenger RNA translation of EBNA1 in cis and that this effect can be distinguished from its effect on proteasomal degradation. Hence, inhibition of messenger RNA translation, but not protein degradation, is essential to prevent antigen presentation on MHC class I molecules. Thus, by minimizing translation of the EBNA1 transcript, cells expressing EBNA1 avoid cytotoxic T cell recognition. At the same time, blocking degradation maintains the EBNA1 expression level.
爱泼斯坦-巴尔病毒编码的核抗原1（EBNA1）的甘氨酸-丙氨酸重复结构域（GAr）可阻止主要组织相容性复合体（MHC）I类限制性的EBNA1表位向细胞毒性T细胞的呈递。此前这种效应被归因于GAr抑制其自身蛋白酶体降解的能力。在此我们在体外和体内均表明，GAr还能顺式抑制EBNA1的信使核糖核酸翻译，且这种效应可与其对蛋白酶体降解的效应相区分。因此，抑制信使核糖核酸翻译而非蛋白质降解对于防止抗原在MHC I类分子上呈递至关重要。这样，通过尽量减少EBNA1转录本的翻译，表达EBNA1的细胞可避免细胞毒性T细胞的识别。同时，阻断降解可维持EBNA1的表达水平。
