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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Interaction of MEQ protein and C-terminal-binding protein is critical for induction of lymphomas by Marek's disease virus
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Interaction of MEQ protein and C-terminal-binding protein is critical for induction of lymphomas by Marek's disease virus

机译：MEQ蛋白和C末端结合蛋白的相互作用对于马立克氏​​病病毒诱导淋巴瘤至关重要

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Marek's disease virus (MDV) is an oncogenic herpesvirus that induces fatal T cell lymphomas in chickens. With more than 20 billion doses of vaccine used annually, vaccination constitutes the cornerstone of Marek's disease control. Despite the success of vaccination, evolution of virulence among MDV strains continues to threaten the effectiveness of the current Marek's disease vaccines. MDV-encoded protein MEQ (MDV EcoRI Q) probably acts as a transcription factor and is considered to be the major MDV oncoprotein. MEQ sequence shows a Pro-Leu-Asp-Leu-Ser (PLDLS) motif known to bind C-terminal-binding protein (CtBP), a highly conserved cellular transcriptional corepressor with roles in the regulation of development, proliferation, and apoptosis. Here we show that MEQ can physically and functionally interact with CtBP through this motif and that this interaction is critical for oncogenesis because mutations in the CtBP-interaction domain completely abolished oncogenicity. This direct role for MEQ-CtBP interaction in MDV oncogenicity highlights the convergent evolution of molecular mechanisms of neoplastic transformation by herpesviruses because Epstein-Barr virus oncoproteins EBNA 3A and 3C also interact with CtBP. We also demonstrate that the nononcogenic MDV generated by mutagenesis of the CtBP-interaction domain of MEQ has the potential to be an improved vaccine against virulent MDV infection. Engineering MDV with precisely defined attenuating mutations, therefore, represents an effective strategy for generating new vaccines against this major poultry disease.
机译：马立克氏病病毒（MDV）是一种致癌性疱疹病毒，可诱发鸡的致命T细胞淋巴瘤。每年使用超过200亿剂疫苗，疫苗接种是Marek疾病控制的基石。尽管疫苗接种成功，但MDV株之间毒力的演变仍威胁着当前马立克氏病疫苗的有效性。 MDV编码的蛋白质MEQ（MDV EcoRI Q）可能是转录因子，被认为是主要的MDV癌蛋白。 MEQ序列显示一个Pro-Leu-Asp-Leu-Ser（PLDLS）基序，已知可与C末端结合蛋白（CtBP）结合，C-BP是一种高度保守的细胞转录共表达因子，在调控发育，增殖和凋亡中发挥作用。在这里，我们表明，MEQ可以通过该基序与CtBP进行物理和功能相互作用，并且这种相互作用对于肿瘤发生至关重要，因为CtBP相互作用域中的突变完全消除了致癌性。 MEQ-CtBP相互作用在MDV致癌性中的这种直接作用突出了疱疹病毒进行的肿瘤转化的分子机制的趋同进化，因为爱泼斯坦-巴尔病毒癌蛋白EBNA 3A和3C也与CtBP相互作用。我们还证明了通过MEQ的CtBP相互作用域的诱变产生的非致癌性MDV有潜力成为针对有毒的MDV感染的改良疫苗。因此，具有精确定义的减毒突变的工程MDV代表了一种针对这种主要家禽疾病产生新疫苗的有效策略。

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