Zhao Ling-Jun, Loewenstein Paul M, Green Maurice
Department of Microbiology and Molecular Immunology/Institute for Molecular Virology, Saint Louis University School of Medicine, Doisy Research Center, Rm 633, 1205 Carr Lane, St. Louis, MO 63104, USA.
Department of Microbiology and Molecular Immunology/Institute for Molecular Virology, Saint Louis University School of Medicine, Doisy Research Center, Rm 633, 1205 Carr Lane, St. Louis, MO 63104, USA.
Virology. 2017 Dec;512:172-179. doi: 10.1016/j.virol.2017.08.010. Epub 2017 Sep 28.
Cellular transformation by adenovirus E1A requires targeting TRRAP, a scaffold protein which helps assemble histone acetyltransferase complexes, including the NuA4 complex. We recently reported that E1A and E1A 1-80 (N-terminal 80 aa) promote association of the proto-oncogene product MYC with the NuA4 complex. The E1A N-terminal TRRAP-targeting (ET) domain is required for E1A 1-80 to interact with the NuA4 complex. We demonstrate that an ET-MYC fusion associates with the NuA4 complex more efficiently than does MYC alone. Because MYC regulates genes for multiple cellular pathways, we performed global RNA-sequence analysis of cells expressing MYC or ET-MYC, and identified a panel of genes (262) preferentially activated by ET-MYC and significantly enriched in genes involved in gene expression and ribosome biogenesis, suggesting that E1A enhances MYC association with the NuA4 complex to activate a set of MYC target genes likely involved in cellular proliferation and cellular transformation by E1A and by MYC.
腺病毒E1A介导的细胞转化需要靶向TRRAP，TRRAP是一种支架蛋白，有助于组装包括NuA4复合物在内的组蛋白乙酰转移酶复合物。我们最近报道，E1A和E1A 1-80（N端80个氨基酸）促进原癌基因产物MYC与NuA4复合物的结合。E1A N端TRRAP靶向（ET）结构域是E1A 1-80与NuA4复合物相互作用所必需的。我们证明，ET-MYC融合蛋白与NuA4复合物的结合比单独的MYC更有效。由于MYC调节多种细胞途径的基因，我们对表达MYC或ET-MYC的细胞进行了全基因组RNA序列分析，并鉴定出一组基因（262个），这些基因优先被ET-MYC激活，并且在参与基因表达和核糖体生物发生的基因中显著富集，这表明E1A增强了MYC与NuA4复合物的结合，以激活一组可能参与E1A和MYC介导的细胞增殖和细胞转化的MYC靶基因。
