Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore MD 21205, USA.
Virology. 2011 Aug 15;417(1):161-8. doi: 10.1016/j.virol.2011.05.017. Epub 2011 Jun 22.
The adenovirus E4 11 k protein, product of E4 ORF3, is required in infection for processes including normal accumulation of viral late mRNAs. 11 k restructures both the nucleus and cytoplasm of infected cells by relocalizing specific host cell target proteins, most strikingly components of nuclear PML oncogenic domains. It is likely that in many cases relocalization inactivates target proteins to produce 11 k's effects, although the mechanism and targets for stimulation of late mRNA accumulation is unknown. We have identified a new set of proteins relocalized by 11 k: at least five protein components of cytoplasmic mRNA processing bodies (p-bodies) are found in 11 k-induced cytoplasmic aggresomes, sites where proteins are inactivated or destroyed. One of these p-body proteins, RNA helicase Ddx6, binds 11 k, suggesting a mechanism for relocalization. Because p-bodies are sites for mRNA degradation, their modification by 11 k may provide an explanation for the role of 11 in viral late mRNA accumulation.
腺病毒 E4 11 k 蛋白是 E4 ORF3 的产物,在感染过程中需要正常积累病毒晚期 mRNA。11 k 通过重新定位特定的宿主细胞靶蛋白来重组感染细胞的核和细胞质,最显著的是核 PML 致癌结构域的成分。很可能在许多情况下,重新定位使靶蛋白失活以产生 11 k 的作用,尽管刺激晚期 mRNA 积累的机制和靶标尚不清楚。我们已经鉴定出一组由 11 k 重新定位的新蛋白质:至少有五种细胞质 mRNA 处理体(p 体)的蛋白质成分存在于 11 k 诱导的细胞质聚集物中,这些聚集物是蛋白质失活或破坏的部位。这些 p 体蛋白之一,RNA 解旋酶 Ddx6,与 11 k 结合,提示了一种重新定位的机制。由于 p 体是 mRNA 降解的部位,因此 11 k 对其的修饰可能为 11 在病毒晚期 mRNA 积累中的作用提供了一种解释。