C-Jun, activated by various extracellular signals, is important for cell differentiation, proliferation, apoptosis, and inflammatory responses. We have previously reported that bovine herpesvirus 1 (BoHV-1) infection in MDBK cells stimulates the c-Jun NH2-terminal kinase (JNK)/c-Jun cascade for efficient replication. However, the mechanisms regarding the regulation of c-Jun following BoHV-1 infection remain unknown. In this study, we show that virus infection increases accumulation of p-c-Jun(S73) (phosphorylated c-Jun at Ser73) and p-β-catenin(S552) in the nucleus, resulting in relocalized nuclear p-c-Jun(S73) to assemble in highlighted punctum via a confocal microscope assay. An association between β-catenin and c-Jun in the nucleus was readily detected in virus-infected, but not mock-infected cells. Interestingly, β-catenin was found to be involved in the regulation of c-Jun signaling in virus-infected cells as iCRT14, a β-catenin-specific inhibitor that can inhibit β-catenin-dependent transcriptional activity, was able to decrease protein expression and phosphorylation of c-Jun. Furthermore, we suggest that BoHV-1 infection stimulates c-Jun phosphorylation regulated by β-catenin via both c-Jun NH2-terminal kinase (JNK)-dependent and JNK-independent mechanisms. These data add to our knowledge regarding the regulation of c-Jun following virus infection and further support the important roles of β-catenin signaling playing in BoHV-1 infection.

C-Jun被各种细胞外信号激活，对于细胞分化，增殖，凋亡和炎症反应很重要。我们以前曾报道过，MDBK细胞中的牛疱疹病毒1（BoHV-1）感染会刺激c-Jun NH2末端激酶（JNK）/ c-Jun级联以进行有效复制。然而，有关BoHV-1感染后c-Jun调控的机制仍不清楚。在这项研究中，我们表明病毒感染会增加pc-Jun（S73）（在Ser73处磷酸化的c-Jun）和p-β-catenin（S552）在细胞核中的积累，从而使pc-Jun（S73）核重新定位为通过共聚焦显微镜分析以高亮点的形式组装。在病毒感染但非模拟感染的细胞中很容易检测到β-catenin和细胞核中的c-Jun之间的关联。有趣的是 发现β-catenin参与了病毒感染细胞中c-Jun信号的调控，因为iCRT14是一种β-catenin特异性抑制剂，可以抑制β-catenin依赖的转录活性，能够降低蛋白质表达和磷酸化。 c-Jun。此外，我们建议BoHV-1感染通过c-Jun NH2末端激酶（JNK）依赖和JNK独立的机制刺激β-连环蛋白调节的c-Jun磷酸化。这些数据增加了我们对病毒感染后c-Jun调控的认识，并进一步支持了β-catenin信号在BoHV-1感染中的重要作用。能够降低c-Jun的蛋白质表达和磷酸化。此外，我们建议BoHV-1感染通过c-Jun NH2末端激酶（JNK）依赖和JNK独立的机制刺激β-连环蛋白调节的c-Jun磷酸化。这些数据增加了我们对病毒感染后c-Jun调控的认识，并进一步支持了β-catenin信号在BoHV-1感染中的重要作用。能够降低c-Jun的蛋白质表达和磷酸化。此外，我们建议BoHV-1感染通过c-Jun NH2末端激酶（JNK）依赖和JNK独立的机制刺激β-连环蛋白调节的c-Jun磷酸化。这些数据增加了我们对病毒感染后c-Jun调控的认识，并进一步支持了β-catenin信号在BoHV-1感染中的重要作用。