Cap-dependent binding of mRNA to the 40 S ribosomal subunit during translational initiation requires the association of eukaryotic initiation factor 4G (eIF4G; formerly eIF-4 and p220) with other initiation factors, notably eIF4E, eIF4A, and eIF3. Infection of cells by picornaviruses results in proteolytic cleavage of eIF4G and generation of a cap-independent translational state. Rhinovirus 2A protease and foot-and-mouth-disease virus L protease were used to analyze the association of eIF4G with eIF4A, eIF4E, and eIF3. Both proteases bisect eIF4G into N- and C-terminal fragments termed cp and cp. cp was shown to contain the eIF4E-binding site, as judged by retention on mGTP-Sepharose, whereas cp was bound to eIF3 and eIF4A, based on ultracentrifugal co-sedimentation. Further proteolysis of cp by L protease produced an 18-kDa polypeptide termed cp which retained eIF4E binding activity and corresponded to amino acid residues 319-479 of rabbit eIF4G. Further proteolysis of cp yielded several smaller fragments. cp (887-1402) contained the eIF4A binding site, whereas cp (480-886) contained the eIF3 binding site. These results suggest that cleavage by picornaviral proteases at residues 479-486 separates eIF4G into two domains, one required for recruiting capped mRNAs and one for attaching mRNA to the ribosome and directing helicase activity. Only the latter would appear to be necessary for internal initiation of picornaviral RNAs.

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				T. Aragón, S. de la Luna, I. Novoa, L. Carrasco, J. Ortín, and A. Nieto Eukaryotic Translation Initiation Factor 4GI Is a Cellular Target for NS1 Protein, a Translational Activator of Influenza Virus Mol. Cell. Biol., September 1, 2000; 20(17): 6259 - 6268. [Abstract] [Full Text]

				I. B. Lomakin, C. U. T. Hellen, and T. V. Pestova Physical Association of Eukaryotic Initiation Factor 4G (eIF4G) with eIF4A Strongly Enhances Binding of eIF4G to the Internal Ribosomal Entry Site of Encephalomyocarditis Virus and Is Required for Internal Initiation of Translation Mol. Cell. Biol., August 15, 2000; 20(16): 6019 - 6029. [Abstract] [Full Text]

				L. Aravind and E. V. Koonin Eukaryote-specific Domains in Translation Initiation Factors: Implications for Translation Regulation and Evolution of the Translation System Genome Res., August 1, 2000; 10(8): 1172 - 1184. [Abstract] [Full Text]

				L. O. Roberts, A. J. Boxall, L. J. Lewis, G. J. Belsham, and G. E. N. Kass Caspases are not involved in the cleavage of translation initiation factor eIF4GI during picornavirus infection J. Gen. Virol., July 1, 2000; 81(7): 1703 - 1707. [Abstract] [Full Text]

				M. Gale Jr., S.-L. Tan, and M. G. Katze Translational Control of Viral Gene Expression in Eukaryotes Microbiol. Mol. Biol. Rev., June 1, 2000; 64(2): 239 - 280. [Abstract] [Full Text] [PDF]

				G. N. Rao Oxidant Stress Stimulates Phosphorylation of eIF4E without an Effect on Global Protein Synthesis in Smooth Muscle Cells. LACK OF EVIDENCE FOR A ROLE OF H2O2 IN ANGIOTENSIN II-INDUCED HYPERTROPHY J. Biol. Chem., May 26, 2000; 275(22): 16993 - 16999. [Abstract] [Full Text] [PDF]

				T. Ohlmann, M. Lopez-Lastra, and J.-L. Darlix An Internal Ribosome Entry Segment Promotes Translation of the Simian Immunodeficiency Virus Genomic RNA J. Biol. Chem., April 14, 2000; 275(16): 11899 - 11906. [Abstract] [Full Text] [PDF]

				B. D. Keiper, B. J. Lamphear, A. M. Deshpande, M. Jankowska-Anyszka, E. J. Aamodt, T. Blumenthal, and R. E. Rhoads Functional Characterization of Five eIF4E Isoforms in Caenorhabditis elegans J. Biol. Chem., March 31, 2000; 275(14): 10590 - 10596. [Abstract] [Full Text] [PDF]

				A. Barco, E. Feduchi, and L. Carrasco A Stable HeLa Cell Line That Inducibly Expresses Poliovirus 2Apro: Effects on Cellular and Viral Gene Expression J. Virol., March 1, 2000; 74(5): 2383 - 2392. [Abstract] [Full Text]

				M. Stoneley, S. A. Chappell, C. L. Jopling, M. Dickens, M. MacFarlane, and A. E. Willis c-Myc Protein Synthesis Is Initiated from the Internal Ribosome Entry Segment during Apoptosis Mol. Cell. Biol., February 15, 2000; 20(4): 1162 - 1169. [Abstract] [Full Text]

				D. Goldstaub, A. Gradi, Z. Bercovitch, Z. Grosmann, Y. Nophar, S. Luria, N. Sonenberg, and C. Kahana Poliovirus 2A Protease Induces Apoptotic Cell Death Mol. Cell. Biol., February 15, 2000; 20(4): 1271 - 1277. [Abstract] [Full Text]

				S. Morino, H. Imataka, Y. V. Svitkin, T. V. Pestova, and N. Sonenberg Eukaryotic Translation Initiation Factor 4E (eIF4E) Binding Site and the Middle One-Third of eIF4GI Constitute the Core Domain for Cap-Dependent Translation, and the C-Terminal One-Third Functions as a Modulatory Region Mol. Cell. Biol., January 15, 2000; 20(2): 468 - 477. [Abstract] [Full Text]

				S. Henis-Korenblit, N. L. Strumpf, D. Goldstaub, and A. Kimchi A Novel Form of DAP5 Protein Accumulates in Apoptotic Cells as a Result of Caspase Cleavage and Internal Ribosome Entry Site-Mediated Translation Mol. Cell. Biol., January 15, 2000; 20(2): 496 - 506. [Abstract] [Full Text]

				G. J. Belsham, G. M. McInerney, and N. Ross-Smith Foot-and-Mouth Disease Virus 3C Protease Induces Cleavage of Translation Initiation Factors eIF4A and eIF4G within Infected Cells J. Virol., January 1, 2000; 74(1): 272 - 280. [Abstract] [Full Text]

				M. Niepel and D. R. Gallie Identification and Characterization of the Functional Elements within the Tobacco Etch Virus 5' Leader Required for Cap-Independent Translation J. Virol., November 1, 1999; 73(11): 9080 - 9088. [Abstract] [Full Text] [PDF]

				M. M. Elgadi and J. R. Smiley Picornavirus Internal Ribosome Entry Site Elements Target RNA Cleavage Events Induced by the Herpes Simplex Virus Virion Host Shutoff Protein J. Virol., November 1, 1999; 73(11): 9222 - 9231. [Abstract] [Full Text] [PDF]