Frost Jasmine Rae, Olanubi Oladunni, Cheng Stephen Ka-Hon, Soriano Andrea, Crisostomo Leandro, Lopez Alennie, Pelka Peter
Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB, Canada, R3T 2N2.
General Byng School, 1250 Beaumont St., Winnipeg, MB, Canada, R3T 0L8.
Virology. 2017 Jan;500:11-21. doi: 10.1016/j.virol.2016.10.004. Epub 2016 Oct 19.
Human adenovirus infects terminally differentiated cells and to replicate it must induce S-phase. The chief architects that drive adenovirus-infected cells into S-phase are the E1A proteins, with 5 different isoforms expressed during infection. E1A remodels the infected cell by associating with cellular factors and modulating their activity. The C-terminus of E1A is known to bind to only a handful of proteins. We have identified a novel E1A C-terminus binding protein, Ku70 (XRCC6), which was found to bind directly within the CR4 of E1A from human adenovirus type 5. Depletion of Ku70 reduced virus growth, possibly by activating the DNA damage response pathway. Ku70 was found to localize to viral replication centers and associate with the viral genome. Ku70 was also recruited to cellular cell cycle regulated promoters following viral infection. Our study has identified, for the first time, Ku70 as a novel E1A-binding protein which affects virus life cycle.
人腺病毒感染终末分化细胞，为进行复制必须诱导细胞进入S期。驱动腺病毒感染细胞进入S期的主要因子是E1A蛋白，感染期间可表达5种不同的亚型。E1A通过与细胞因子结合并调节其活性来重塑受感染细胞。已知E1A的C末端仅与少数几种蛋白质结合。我们鉴定出一种新型的E1A C末端结合蛋白Ku70（XRCC6），发现它直接与人5型腺病毒E1A的CR4区域结合。Ku70的缺失可能通过激活DNA损伤反应途径而降低病毒生长。发现Ku70定位于病毒复制中心并与病毒基因组相关联。病毒感染后，Ku70也被募集到细胞周期调控的启动子处。我们的研究首次鉴定出Ku70是一种影响病毒生命周期的新型E1A结合蛋白。
