鉴定一种与癌症相关的 EBV EBNA1 变异体，揭示了其与 PLOD1 和 PLOD3 的一种新的相互作用。

Characterization of a cancer-associated Epstein-Barr virus EBNA1 variant reveals a novel interaction with PLOD1 and PLOD3.

机构信息

Department of Molecular Genetics, University of Toronto, 661 University Ave, Suite 1600, Toronto, ON, M5G 1M1, Canada.

Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.

出版信息

Virology. 2021 Oct;562:103-109. doi: 10.1016/j.virol.2021.07.009. Epub 2021 Jul 21.

DOI:10.1016/j.virol.2021.07.009

PMID:34304093

Abstract

Whole genome sequence analysis of Epstein-Barr virus genomes from tumours and healthy individuals identified three amino acid changes in EBNA1 that are strongly associated with gastric carcinoma and nasopharyngeal carcinoma. Here we show that, while these mutations do not impact EBNA1 plasmid maintenance function, one of them (Thr85Ala) decreases transcriptional activation and results in a gain of function interaction with PLOD1 and PLOD3. PLOD family proteins are strongly linked to multiple cancers, and PLOD1 is recognized as a prognostic marker of gastric carcinoma. We identified the PLOD1 binding site in EBNA1as the N-terminal transactivation domain and show that lysine 83 is critical for this interaction. The results provide a novel link between EBV infection and the cancer-associated PLOD proteins.

摘要

对肿瘤和健康个体中的 Epstein-Barr 病毒基因组进行全基因组序列分析，鉴定出 EBNA1 中的三个氨基酸变化，这些变化与胃癌和鼻咽癌强烈相关。在这里，我们表明，虽然这些突变不影响 EBNA1 质粒的维持功能，但其中一个突变（Thr85Ala）降低了转录激活作用，并导致与 PLOD1 和 PLOD3 的功能获得性相互作用。PLOD 家族蛋白与多种癌症密切相关，PLOD1 被认为是胃癌的预后标志物。我们确定了 EBNA1 中的 PLOD1 结合位点为 N 端转录激活结构域，并表明赖氨酸 83 对这种相互作用至关重要。研究结果为 EBV 感染与癌症相关的 PLOD 蛋白之间提供了新的联系。