Gingras A C, Sonenberg N
Department of Biochemistry and McGill Cancer Center, McGill University, Montréal, Québec, H3G 1Y6, Canada.
Virology. 1997 Oct 13;237(1):182-6. doi: 10.1006/viro.1997.8757.
Infection with many viruses results in the selective shutoff of host protein synthesis. A common target for virus interference with host protein synthesis is the cap-binding protein complex, eIF4F. The large subunit of the complex, eIF4G, is cleaved upon picornavirus (except cardiovirus) infection. Infection with adenovirus and influenza virus causes dephosphorylation of the cap-binding subunit, eIF4E. Recently, it has been shown that infection with poliovirus or encephalomyocarditis virus activates 4E-BP1, which is a specific inhibitor of eIF4E. Here we show that early in adenovirus infection, 4E-BP1 and its related protein 4E-BP2 are phosphorylated and hence inactivated. This is not consistent with a role of 4E-BPs in adenovirus-induced shutoff, but could explain the increase in protein synthesis reported early in infection. Phosphorylation of 4E-BP1 and 4E-BP2 is consistent with earlier findings in adenovirus-infected cells on the activation of the protein kinase p70(S6k), whose phosphorylation lies on the same pathway as 4E-BPs, by E1A. Findings similar to those described here were reported for 4E-BP1 by D. Feigenblum and R. J. Schneider (1996, Mol. Cell. Biol. 16, 5450-5457).
许多病毒感染会导致宿主蛋白质合成的选择性关闭。病毒干扰宿主蛋白质合成的一个常见靶点是帽结合蛋白复合物eIF4F。该复合物的大亚基eIF4G在小核糖核酸病毒（心肌炎病毒除外）感染时会被切割。腺病毒和流感病毒感染会导致帽结合亚基eIF4E发生去磷酸化。最近研究表明，脊髓灰质炎病毒或脑心肌炎病毒感染会激活4E-BP1，它是eIF4E的一种特异性抑制剂。在此我们发现，在腺病毒感染早期，4E-BP1及其相关蛋白4E-BP2会发生磷酸化，从而失活。这与4E-BP在腺病毒诱导的蛋白质合成关闭中的作用不一致，但可以解释感染早期报道的蛋白质合成增加现象。4E-BP1和4E-BP2的磷酸化与腺病毒感染细胞中早期关于蛋白激酶p70(S6k)激活的研究结果一致，p70(S6k)的磷酸化与4E-BP处于同一信号通路，由E1A激活。D. Feigenblum和R. J. Schneider（1996年，《分子与细胞生物学》16卷，5450 - 5457页）报道了与本文所述类似的关于4E-BP1研究结果。
