PDF(Pubmed)
Abstract：
Foamy viruses are members of the Retroviridae family\'s Spumaretrovirinae subfamily. They induce cell vacuolation and exhibit a foamy pathogenic impact after infecting cells. DACH1 (dachshund family transcription factor 1) is a crucial cytokine linked to tumor development, and is associated with the growth of many different malignant tumor cells. Additionally, DACH1 suppresses pancreatic cell proliferation and is involved in diabetes insulin signaling. Prototype foamy viruses (PFVs) were used for the investigation of the regulatory mechanism of FVs on cellular DACH1 expression. The results show that DACH1 expression in PFV-infected cells was inconsistent at both the transcriptional and protein levels. At the transcriptional level, DACH1 was significantly activated by PFV transactivator Tas, and dual-luciferase reporter gene tests, EMSA, and ChIP assays found a Tas response element of 21 nucleotides in the DACH1 promoter. PFV and Tas did not boost the levels of DACH1 protein in a manner consistent with the high levels of DACH1 transcription expression. It was noted that Tas increased the expression of the Ser/Thr protein phosphatase PPM1E, causing PPM1E-mediated post-translational SUMOylation alterations of DACH1 to prompt DACH1 to degrade. The reason for DACH1 protein degradation is that DACH1 inhibits PFV replication. To sum up, these findings show that PFV upregulated the transcription of DACH1, while urging its protein into PPM1E-mediated SUMOylation, to eliminate the adverse effect of DACH1 overexpression of host cells on viral replication and promote virus survival.
摘要：
泡沫病毒是逆转录病毒科的Spumaretrovirinae亚科的成员。它们诱导细胞空泡化，并在感染细胞后表现出泡沫致病作用。DACH1(dachshund家族转录因子1)是与肿瘤发展相关的关键细胞因子，并与许多不同恶性肿瘤细胞的生长有关。此外,DACH1抑制胰腺细胞增殖并参与糖尿病胰岛素信号传导。原型泡沫病毒（PFV）用于研究FV对细胞DACH1表达的调节机制。结果表明，DACH1在PFV感染的细胞中的表达在转录和蛋白质水平上都不一致。在转录水平，DACH1被PFV反式激活剂Tas显著激活，和双荧光素酶报告基因测试，EMSA,和ChIP测定在DACH1启动子中发现了21个核苷酸的Tas反应元件。PFV和Tas没有以与DACH1转录表达高水平一致的方式提高DACH1蛋白的水平。注意到Tas增加了Ser/Thr蛋白磷酸酶PPM1E的表达，引起PPM1E介导的DACH1翻译后亚糖基化改变，促使DACH1降解。DACH1蛋白降解的原因是DACH1抑制PFV复制。总而言之,这些发现表明PFV上调DACH1的转录，同时促使其蛋白进入PPM1E介导的SUMO化，消除DACH1过表达宿主细胞对病毒复制的不良影响,促进病毒存活。
