通过PLOD1 lysine hydroxylase调节EBNA1蛋白稳定性和DNA复制活性
Jayaraju Dheekollu1, Andreas Wiedmer1, Samantha S Soldan1
1The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
PLoS pathogens
|June 1, 2023
概括
聚合物氨酸二氧化酶1 (PLOD1) 调节爱斯坦-巴尔核抗原1 (EBNA1) 的稳定性和功能. 对于EBNA1在病毒复制,发作维护和宿主细胞存活中的作用来说,PLOD1的相互作用至关重要.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 爱斯坦-巴尔病毒 (EBV) 与癌症和自身免疫性疾病有关.
- 爱斯坦-巴尔核抗原1 (EBNA1) 对于EBV DNA复制和在潜伏期间维护病例至关重要.
- 调节EBNA1蛋白的稳定性和功能的机制尚不清楚.
研究的目的:
- 研究控制EBNA1蛋白稳定性的机制.
- 确定EBNA1相互作用蛋白及其在EBV生物学中的作用.
- 了解EBNA1稳定性如何影响病毒复制和宿主细胞存活.
主要方法:
- 蛋白质组分析以确定EBNA1的相互作用伙伴.
- 通过使用shRNA和小分子抑制剂来减轻公素氨酸-2氧化酸-5二氧化酶1 (PLOD1) 的耗尽.
- 质谱测量以确定EBNA1.1上的翻译后修改.
- 在EBNA1 lysine残留物 (K460,K461) 的位点定向突变发生 (K460,K461).
主要成果:
- 蛋白质组分析显示,EBNA1与PLOD蛋白家族相互作用,特别是PLOD1.
- 减少或抑制PLOD1导致EBNA1蛋白水平降低和选择性抑制EBV阳性淋巴细胞的生长.
- 由于PLOD1的枯竭,EBV病例消失,ORIP依赖DNA复制受损.
- 质谱测量确定了EBNA1.1.上的K460/K461的基化. K460的突变破坏了ORIP复制,而K460/K461的突变降低了EBNA1的稳定性和PLOD1的相互作用.
结论:
- PLOD1是EBNA1.1的一个新型交互合作伙伴.
- PLOD1调节EBNA1蛋白的稳定性及其在病毒DNA复制和插曲维护中的功能.
- 针对PLOD1-EBNA1相互作用可能为EBV相关疾病提供治疗策略.
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