通过活细胞成像分析腺病毒E4orf4蛋白对H1299肿瘤细胞有丝分裂进程的影响。
Analysis by live imaging of effects of the adenovirus E4orf4 protein on passage through mitosis of H1299 tumor cells.
作者信息
Sriskandarajah Neera, Blanchette Paola, Kucharski Thomas J, Teodoro Jose G, Branton Philip E
机构信息
Department of Biochemistry, McGill University, Montreal, Québec, Canada Goodman Cancer Research Centre, McGill University, Montreal, Québec, Canada.
Department of Biochemistry, McGill University, Montreal, Québec, Canada.
出版信息
J Virol. 2015 Apr;89(8):4685-9. doi: 10.1128/JVI.03437-14. Epub 2015 Feb 4.
Abstract
The adenovirus E4orf4 protein expressed at high levels kills cancer cells but not normal human primary cells. Previous studies suggested that disruption of processes that regulate mitosis may underlie E4orf4 toxicity. Here we have used live imaging to show that E4orf4 induces a slowed defective transit through mitosis, exhibiting a delay or often failure in cytokinesis that may account for an accumulation of G1 tetraploids in the population of dying E4orf4-expressing cells.
摘要
高水平表达的腺病毒E4orf4蛋白可杀死癌细胞，但不会杀死正常人类原代细胞。先前的研究表明，调节有丝分裂的过程受到破坏可能是E4orf4毒性的基础。在此，我们利用实时成像技术表明，E4orf4会导致有丝分裂过程中出现缓慢的缺陷性进程，表现为胞质分裂延迟或常常失败，这可能是导致表达E4orf4的死亡细胞群体中G1四倍体积累的原因。
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2
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PLoS Pathog. 2013;9(11):e1003742. doi: 10.1371/journal.ppat.1003742. Epub 2013 Nov 14.
3
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