MODIFICATION OF PROTEIN-SYNTHESIS INITIATION-FACTORS AND THE SHUT-OFF OF HOST PROTEIN-SYNTHESIS IN ADENOVIRUS-INFECTED CELLS
MODIFICATION OF PROTEIN-SYNTHESIS INITIATION-FACTORS AND THE SHUT-OFF OF HOST PROTEIN-SYNTHESIS IN ADENOVIRUS-INFECTED CELLS
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DOI：
10.1016/0042-6822(89)90409-1
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发表时间：
1989-01-01
期刊：
影响因子：
3.7
通讯作者：
MATHEWS, MB
中科院分区：
文献类型：
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作者：
OMALLEY, RP;DUNCAN, RF;MATHEWS, MB
大量主要来自细胞提取物研究的数据表明，腺病毒感染细胞中的蛋白质合成在感染后期需要VA RNA1，以防止一种被称为DAI的蛋白激酶的激活以及起始因子eIF - 2的α亚基随后的磷酸化。为了验证这一结论，我们测量了感染野生型病毒（Ad2）和一种不产生VA RNA1的突变体（Ad5dl331）的细胞中eIF - 2α磷酸化的稳态水平。与所提出的机制一致，在感染Ad5dl331后期，α亚基被高度磷酸化（约90%）。令人惊讶的是，在感染Ad2后期，eIF - 2α磷酸化也增加（至约30%），这表明VA RNA和DAI可能参与病毒mRNA的选择性翻译以及在后期宿主细胞蛋白质合成的关闭。与该模型一致，在低水平表达DAI的细胞中，宿主蛋白质合成的关闭存在缺陷。
A substantial body of data, largely derived from study of cell extracts, indicates that protein synthesis in adenovirus-infected cells requires VA RNAl at late times of infection to prevent the activation of a protein kinase known as DAI, and the consequent phosphorylation of the .alpha.-subunit of initiation factor eIF-2. To verify this conclusion, we have measured the steady-state levels of eIF-2.alpha. phosphorylation in cells infected with wild-type virus (Ad2) and a mutant that produces no VA RNAl (Ad5dl331). Consistent with the proposed mechanism, the .alpha.-subunit was very highly phosphorylated (.apprx. 90%) at late times of infection with Ad5dl331. Surprisingly, eIF-2.alpha. phosphorylation also increased (to .apprx. 30%) at late times of infection with Ad2, suggesting that VA RNA and DAI might be involved in the selective translation of viral mRNA and the shut-off of host cell protein synthesis during the late phase. In agreement with this model, host protein synthesis shut-off is defective in cells expressing low levels of DAI.