Viral protein R (Vpr) is an accessory protein found in various primate lentiviruses, including human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) as well as simian immunodeficiency viruses (SIVs). Vpr modulates many processes during viral lifecycle via interaction with several of cellular targets. Previous studies showed that HIV-1 Vpr strengthened degradation of Mini-chromosome Maintenance Protein10 (MCM10) by manipulating DCAF1-Cul4-E3 ligase in proteasome-dependent pathway. However, whether Vpr from other primate lentiviruses are also associated with MCM10 degradation and the ensuing impact remain unknown. Based on phylogenetic analyses, a panel of primate lentiviruses Vpr/x covering main virus lineages was prepared. Distinct MCM10 degradation profiles were mapped and HIV-1, SIVmus and SIVrcm Vprs induced MCM10 degradation in proteasome-dependent pathway. Colocalization and interaction between MCM10 with these Vprs were also observed. Moreover, MCM10 2-7 interaction region was identified as a determinant region susceptible to degradation. However, MCM10 degradation did not alleviate DNA damage response induced by these Vpr proteins. MCM10 degradation by HIV-1 Vpr proteins was correlated with G2/M arrest, while induction of apoptosis and oligomerization formation of Vpr failed to alter MCM10 proteolysis. The current study demonstrated a distinct interplay pattern between primate lentiviruses Vpr proteins and MCM10.

中文翻译：

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灵长类慢病毒Vpr蛋白的独特MCM10蛋白酶降解特性。

病毒蛋白R（Vpr）是在各种灵长类慢病毒中发现的辅助蛋白，包括人类1型和2型人类免疫缺陷病毒（HIV-1和HIV-2）以及猿猴免疫缺陷病毒（SIV）。Vpr通过与几个细胞靶标相互作用来调节病毒生命周期中的许多过程。先前的研究表明，HIV-1 Vpr通过以蛋白酶体依赖性途径操纵DCAF1-Cul4-E3连接酶来增强微型染色体维持蛋白10（MCM10）的降解。但是，来自其他灵长类慢病毒的Vpr是否也与MCM10降解有关，其影响尚不清楚。基于系统发育分析，制备了覆盖主要病毒谱系的一组灵长类慢病毒Vpr / x。绘制了不同的MCM10降解曲线，并绘制了HIV-1，SIVmus和SIVrcm Vprs通过蛋白酶体依赖性途径诱导MCM10降解。还观察到MCM10与这些Vpr之间的共定位和相互作用。此外，MCM10 2-7相互作用区域被确定为易降解的决定性区域。但是，MCM10降解并不能减轻这些Vpr蛋白诱导的DNA损伤反应。HIV-1 Vpr蛋白降解MCM10与G2 / M阻滞有关，而Vpr的凋亡诱导和寡聚形成未能改变MCM10蛋白水解。当前的研究表明灵长类慢病毒Vpr蛋白和MCM10之间存在明显的相互作用。但是，MCM10降解并不能减轻这些Vpr蛋白诱导的DNA损伤反应。HIV-1 Vpr蛋白降解MCM10与G2 / M阻滞有关，而Vpr的凋亡诱导和寡聚形成未能改变MCM10蛋白水解。当前的研究表明灵长类慢病毒Vpr蛋白和MCM10之间存在明显的相互作用。但是，MCM10降解并不能减轻这些Vpr蛋白诱导的DNA损伤反应。HIV-1 Vpr蛋白降解MCM10与G2 / M阻滞有关，而Vpr的凋亡诱导和寡聚形成未能改变MCM10蛋白水解。当前的研究表明灵长类慢病毒Vpr蛋白和MCM10之间存在明显的相互作用。