title: Proteolysis of human eukaryotic translation initiation factor eIF4GII, but not eIF4GI, coincides with the shutoff of host protein synthesis after poliovirus infection.
abstract: Eukaryotic initiation factor (eIF) 4GI is a component of the cap-binding protein complex eIF4F, which is required for cap-dependent translation. Infection of cells by poliovirus results in a precipitous decline of host cell protein synthesis, which is preceded by the cleavage of eIF4GI. Cleavage of eIF4GI results in the inhibition of cap-dependent translation. Poliovirus translation is not affected by eIF4GI cleavage, however, because poliovirus mRNA is translated by a cap-independent mechanism. Cleavage of eIF4GI alone cannot explain the shutoff of host protein synthesis, because after infection in the presence of inhibitors of virus replication, eIF4GI is cleaved, yet host protein synthesis is only partially inhibited. Here we show that eIF4GII, a recently discovered functional homolog of eIF4GI, is more resistant to poliovirus-mediated cleavage than eIF4GI, and that its proteolysis is concomitant with the shutoff of host cell protein synthesis. Moreover, infection with poliovirus in the presence of inhibitors of virus replication resulted in efficient cleavage of eIF4GI, but only partial proteolysis of eIF4GII. Thus, cleavage of both eIF4GI and eIF4GII appears to be required for the shutoff of host protein synthesis after poliovirus infection. These results explain several earlier reports documenting the lack of correlation between eIF4GI cleavage and inhibition of cellular mRNA translation after poliovirus infection.
authors.affiliation: Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Drummond Street, Montréal, Québec, Canada, H3G 1Y6.
authors.forename: A
authors.initials: A
authors.lastname: Gradi
authors.forename: Y V
authors.initials: YV
authors.lastname: Svitkin
authors.forename: H
authors.initials: H
authors.lastname: Imataka
authors.forename: N
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D039603:Eukaryotic Initiation Factor-4G; D019791:Guanidine / Q000494:pharmacology; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D017955:Poliovirus / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: C113920:EIF4G1 protein, human; C491300:EIF4G2 protein, human; D039603:Eukaryotic Initiation Factor-4G; D010446:Peptide Fragments; D010448:Peptide Initiation Factors; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D014764:Viral Proteins; D008985:Monensin; D008715:Methionine; D019791:Guanidine