Dantuma N P, Sharipo A, Masucci M G
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Curr Top Microbiol Immunol. 2002;269:23-36. doi: 10.1007/978-3-642-59421-2_2.
Ubiquitin/proteasome-dependent proteolysis is involved in the regulation of a large variety of cellular processes including cell cycle progression, tissue development and atrophy, flux of substrates through metabolic pathways, selective elimination of abnormal proteins and processing of intracellular antigens for major histocompatibility complex (MHC) class I-restricted T-cell responses. Many viruses tamper with this proteolytic machinery by encoding proteins that interact with various components of the pathway. A particularly interesting example of a viral protein that interferes with proteasomal processing is the Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA1). EBNA1 contains an internal repeat exclusively composed of glycines and alanines that inhibits in cis the presentation of MHC class I-restricted T-cell epitopes and prevents ubiquitin/proteasome-dependent proteolysis in vitro and in vivo. The glycine-alanine repeat acts as a transferable element on a variety of proteasomal substrates and may therefore provide a new approach to the modification of cellular proteins for therapeutic purposes.
泛素/蛋白酶体依赖性蛋白水解参与多种细胞过程的调控，包括细胞周期进程、组织发育与萎缩、代谢途径中底物的通量、异常蛋白的选择性清除以及主要组织相容性复合体（MHC）I类限制性T细胞应答中细胞内抗原的加工处理。许多病毒通过编码与该途径各种组分相互作用的蛋白质来干扰这种蛋白水解机制。干扰蛋白酶体加工的病毒蛋白的一个特别有趣的例子是爱泼斯坦-巴尔病毒（EBV）核抗原1（EBNA1）。EBNA1含有一个仅由甘氨酸和丙氨酸组成的内部重复序列，该序列在顺式作用下抑制MHC I类限制性T细胞表位的呈递，并在体外和体内阻止泛素/蛋白酶体依赖性蛋白水解。甘氨酸-丙氨酸重复序列作为多种蛋白酶体底物上的可转移元件，因此可能为出于治疗目的修饰细胞蛋白提供一种新方法。
