Adenovirus infection inactivates the translational inhibitors 4E-BP1 and 4E-BP2.
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).
Gingras
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AC
Department of Biochemistry and McGill Cancer Center, McGill University, Montréal, Québec, H3G 1Y6, Canada.
Sonenberg
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D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D039642:Eukaryotic Initiation Factors; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics*; D014176:Protein Biosynthesis; D012097:Repressor Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C104151:EIF4EBP2 protein, human; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D012097:Repressor Proteins