Chapter 24 : Picornavirus Proteinase-Mediated Shutoff of Host Cell Translation: Direct Cleavage of a Cellular Initiation Factor

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Picornavirus Proteinase-Mediated Shutoff of Host Cell Translation: Direct Cleavage of a Cellular Initiation Factor, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817916/9781555812102_Chap24-1.gif /docserver/preview/fulltext/10.1128/9781555817916/9781555812102_Chap24-2.gif


This chapter discusses the strategy used by picornaviruses belonging to the genera of enteroviruses, rhinoviruses, and aphthoviruses to interfere with host cell protein synthesis. First it describes the mechanism of initiation of capped mRNA and compares it with that of uncapped mRNA. It then discusses the role of the viral proteinases and their cellular targets. Finally it focuses on the effect of specific proteolytic cleavage and its function in the initiation of protein synthesis. There is ample evidence that 2A is the viral proteinase responsible for eIF4G cleavage, which results in the inactivation of cap-dependent translation leading to the shutoff of cellular protein synthesis. In addition, based on the known cleavage sites of 2A of HRV2 and 2A of coxsackievirus B4 in the viral polyprotein, sequence comparisons allowed the prediction of three potential cleavage sites in eIF4G. It has recently been demonstrated using an in vitro translation system that newly synthesized 2A of HRV2 is highly efficient in eIF4G cleavage. The discrepancy was particularly dramatic when viral replication was partially inhibited by guanidine-HCl, 3-methyl quercetin, monensin, or nigericin. In the presence of these inhibitors, eIF4G cleavage was found to be essentially complete, whereas cellular protein synthesis was only partially inhibited. Furthermore, generally the same initiation factors are involved in the translation of both types of mRNAs.

Citation: Kuechler E, Seipelt J, Liebig H, Sommergruber W. 2002. Picornavirus Proteinase-Mediated Shutoff of Host Cell Translation: Direct Cleavage of a Cellular Initiation Factor, p 301-311. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch24

Key Concept Ranking

Hepatitis C virus
Foot-and-mouth disease virus
Viral Capsid Proteins
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Effect of proteolytic cleavage of eIF4G by 2A and Lb: sequestration of the cap-binding domain of eIF4F from the ribosomal initiation complex. The two domains of the eIF4G structure are connected by the hinge region, which is the target of 2A and L. Cleavage by both enzymes sequesters the N-terminal domain comprising the binding sites for eIF4E (attached to the 5′-terminal mG cap structure) and for PABP ([poly(A) binding protein]. The C-terminal domain of eIF4G harboring the eIF4A- and eIF3-binding sites remains attached to the 40S ribosomal complex. Reprinted from reference 97 with permission from Elsevier Science.

Citation: Kuechler E, Seipelt J, Liebig H, Sommergruber W. 2002. Picornavirus Proteinase-Mediated Shutoff of Host Cell Translation: Direct Cleavage of a Cellular Initiation Factor, p 301-311. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Comparison of 2A and of Lb cleavage sites in rabbit eIF4G with that of the respective viral polyproteins. Amino acid sequences at the eIF4GI cleavage sites of 2A and of Lb are indicated. 2A cleavage in the HRV2 polyprotein occurs between the C terminus of the capsid protein VP1 and the Ν terminus of 2A. L cleaves the FMDV polyprotein between the C terminus of L and the Ν terminus of the capsid protein VP4.

Citation: Kuechler E, Seipelt J, Liebig H, Sommergruber W. 2002. Picornavirus Proteinase-Mediated Shutoff of Host Cell Translation: Direct Cleavage of a Cellular Initiation Factor, p 301-311. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch24
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Aldabe, R.,, E. Feduchi,, I. Novoa,, and L. Carrasco. 1995. Expression of 2Apro in mammalian cells: effects on translation. FEBS Lett. 377:15.
2. Alvey, I. C.,, E. E. Wyckoff,, S. F. Yu,, R. Lloyd,, and E. Ehrenfeld. 1991. eis and trans activities of poliovirus 2A protease expressed in Escherichia coli. J. Virol. 65:60776083.
3. Ambros, V.,, and D. Baltimore. 1978. Protein is linked to the 5' end of poliovirus RNA by phosphodiester linkage to tyrosine. J. Biol. Chem. 253:52635266.
4. Ambros, V.,, and D. Baltimore. 1980. Purification and properties of a HeLa cell enzyme able to remove the 5'-terminal protein from poliovirus RNA. J. Biol. Chem. 255:67396744.
5. Ambros, V.,, R. F. Petterson,, and D. Baltimore. 1978. An enzymatic activity in uninfected cells that cleaves the linkage between poliovirion RNA and the 5' terminal protein. Cell 15:14391446.
6. Argos, P.,, G. Kamer,, M. J. H. Nicklin,, and E. Wimmer. 1984. Similarity in gene organization and homology between proteins of animal picornaviruses and a plant comovirus suggest common ancestry of these virus families. Nucleic Acids Res. 12:72517267.
7. Bader, B.,, T. Magin,, S. Freudenmann,, and W. Franke. 1991. Intermediate filaments formed de novo from tailless cytokeratins in the cytoplasm and in the nucleus. J. Cell Biol. 115:12931307.
8. Badorff, C.,, N. Berkely,, S. Mehrotra,, J. W. Talhouk,, R. E. Rhoads,, and K. U. Knowlton. 2000. Enteroviral protease 2A directly cleaves dystrophin and is inhibited by a dystrophin-based substrate analogue. J. Biol. Chem. 275:1119111197.
9. Badorff, C.,, G. H. Lee,, B. J. Lamphear,, M. E. Martone,, K. P. Campbell,, R. E. Rhoads,, and K. U. Knowlton. 1999. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat. Med. 5:320326.
10. Bazan, J. F.,, and R. J. Fletterick. 1988. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proc. Natl. Acad. Sci. USA 85:78727876.
11. Belsham, G. J.,, J. K. Brangwyn,, M. D. Ryan,, C. C. Abrams,, and A. M. King. 1990. Intracellular expression and processing of foot-and-mouth disease virus capsid precursors using vaccinia virus vectors: influence of the L protease. Virology 176:524530.
12. Belsham, G. J.,, and N. Sonenberg. 1996. RNA-protein interactions in regulation of Picornavirus RNA translation. Microbiol. Rev. 60:499511.
13. Bernstein, H. D.,, N. Sonenberg,, and D. Baltimore. 1985. Poliovirus mutant that does not selectively inhibit host cell protein synthesis. Mol. Cell. Biol. 5:29132923.
14. Blom, N.,, J. Hansen,, D. Blaas,, and S. Brunak. 1996. Cleavage site analysis in picornaviral polyproteins: discovering cellular targets by neural networks. Protein Sci. 5: 22032216.
15. Bonneau, A. M.,, and N. Sonenberg. 1987. Proteolysis of the p220 component of the cap-binding protein complex is not sufficient for complete inhibition of host cell protein synthesis after poliovirus infection. J. Virol. 61:986991.
16. Borman, A. M.,, R. Kirchweger,, E. Ziegler,, R. E. Rhoads,, T. Skern,, and K. M. Kean. 1997. eIF4G and its proteolytic cleavage products: effect on initiation of protein synthesis from capped, uncapped, and IRES-containing mRNAs. RNA 3:186196.
17. Bovee, M. L.,, B. J. Lamphear,, R. E. Rhoads,, and R. E. Lloyd. 1998. Direct cleavage of eIF4G by poliovirus 2A protease is inefficient in vitro. Virology 245:241249.
18. Bovee, M. L.,, W. E. Marissen,, M. Zamora,, and R. E. Lloyd. 1998. The predominant eIF-4G-specific activity in poliovirus-infected HeLa cells is distinct from 2A protease. Virology 245:229240.
19. Buckley, B.,, and E. Ehrenfeld. 1987. The cap-binding protein complex in uninfected and poliovirus-infected HeLa cells. J. Biol. Chem. 262:1359913606.
20. Burroughs, J. N.,, D. V. Sangar,, B. E. Clarke,, D. J. Rowlands,, A. Billiau,, and D. Collen. 1984Multiple proteases in foot-and-mouth disease virus replication. J. Virol. 50: 878883.
21. Carrasco, L.,, and J. L. Castrillo,. 1987. The regulation of translation in picornavirus-infected cells, p. 115146. In L. Carrasco (ed.), Mechanisms of Viral Toxicity in Animal Cells. CRC Press, Boca Raton, Fla.
22. Carroll, A. R.,, D. J. Rowlands,, and B. E. Clarke. 1984. The complete nucleotide sequence of the RNA coding for the primary translation product of foot and mouth disease virus. Nucleic Acids Res. 12:24612472.
23. Cheah, K.-C.,, L. E.-C. Leong,, and A. G. Porter. 1990. Site-directed mutagenesis suggests close functional relationship between a human rhinovirus 3C cysteine protease and cellular trypsin-like serine proteases. J. Biol. Chem. 265:71807187.
24. Chen, P. H.,, D. A. Ornelles,, and T. Shenk. 1993. The adenovirus L3 23-kilodalton proteinase cleaves the amino-terminal head domain from cytokeratin 18 and disrupts the cytokeratin network of HeLa cells. J. Virol. 67: 35073514.
25. Davies, M.,, J. Pelletier,, L. Meerovitch,, N. Sonenberg,, and R. J. Kaufman. 1991. The effect of poliovirus protease 2Apro expression on cellular metabolism. J. Biol. Chem. 266:1471414720.
26. Devaney, M. A.,, V. N. Vakharia,, R. E. Lloyd,, E. Ehrenfeld,, and M. J. Grubman. 1988. Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex. J. Virol. 62:44074409.
27. Donnelly, M. L. L.,, D. Gani,, S. Monaghan,, and M. D. Ryan. 1997. The cleavage activities of aphthovirus and cardiovirus 2A proteins. J. Gen. Virol. 78:1321.
28. Ehrenfeld, E., 1996. Initiation of translation by Picornavirus RNAs, p. 549573. In J. W. B. Hershey,, M. B. Mathews,, and N. Sonenberg (ed.), Transiationai Control. Cold Spring Harbor Laboratory Press, Plainview, N.Y.
29. Etchison, D.,, S. C. Milburn,, I. Edery,, N. Sonenberg,, and J. W. Hershey. 1982. Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with proteolysis of a 220,000 dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. J. Biol. Chem. 257:1480614810.
30. Fuchs, E.,, and D. W. Cleveland. 1998. A structural scaffolding of intermediate filaments in health and disease. Science 279:514519.
31. Glaser, W.,, and T. Skern. 2000. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 480:151155.
32. Gorbalenya, A. E.,, V. M. Blinov,, and A. M. Donchenko. 1986. Poliovirus-encoded proteinase 3C: a possible evolutionary link between cellular serine and cysteine proteinase families. FEBS Lett. 194:253257.
33. Gorbalenya, A. E.,, A. P. Donchenko,, V. M. Blinov,, and E. V. Koonin. 1989. Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases: a distinct protein superfamily with a common structural fold. FEBS Lett. 243:103114.
34. Gradi, A.,, H. Imataka,, Y. V. Svitkin,, E. Rom,, B. Raught,, S. Morino,, and N. Sonenberg. 1998. A novel functional human eukaryotic translation initiation factor 4G. Mol. Cell. Biol. 18:334342.
35. Gradi, A.,, Y. V. Svitkin,, H. Imataka,, and N. Sonenberg. 1998. Proteolysis of human eukaryotic translation initiation factor eIF4GII, but not eIF4GI, coincides with the shut off of host protein synthesis after poliovirus infection. Proc. Natl. Acad. Sci. USA 95:1108911094.
36. Guarné, A.,, J. Tormo,, R. Kirchweger,, D. Pfistermüller,, I. Fita,, and T. Skern. 1998. Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and elF4G recognition. EMBO J. 17:74697479.
37. Haghigat, A.,, and N. Sonenberg. 1997. eIF4G dramatically enhances the binding of eIF4E to the mRNA 5'-cap structure. J. Biol. Chem. 272:2167721680.
38. Haghigat, A.,, Y. Svitkin,, I. Novoa,, E. Kuechler,, T. Skern,, and N. Sonenberg. 1996. The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase. J. Virol. 70:84448450.
39. Harber, J. J.,, J. Bradley,, C. W. Anderson,, and E. Wimmer. 1991. Catalysis of poliovirus VP0 maturation cleavage is not mediated by serine 10 of VP2. J. Virol. 65:326334.
40. Harris, K. S.,, C. U. T. Hellen,, and E. Wimmer. 1990. Proteolytic processing in the replication of picornaviruses. Semin. Virol. 1:323333.
41. Hellen, C. U. T.,, M. Fäcke,, H.-G. Kräusslich,, C.-K. Lee,, and E. Wimmer. 1991. Characterization of poliovirus 2A proteinase by mutational analysis: residues required for autocatalytic activity are essential for induction of cleavage of eukaryotic initiation factor 4F polypeptide p220. J. Virol. 65:42264231.
42. Hellen, C. U. T.,, C. K. Lee,, and E. Wimmer. 1992. Determinants of substrate recognition by poliovirus 2A proteinase. J. Virol. 66:33303336.
43. Hentze, M. W. 1997. eIF4G: a multipurpose ribosome adapter? Science 275:500501.
44. Hunt, S. L.,, T. Skern,, H.-D. Liebig,, E. Kuechler,, and R. J. Jackson. 1999. Rhinovirus 2A proteinase mediated stimulation of rhinovirus RNA translation is additive to the stimulation effected by cellular RNA binding proteins. Virus Res. 62:119128.
45. Imataka, H.,, A. Gradi,, and N. Sonenberg. 1998. A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. EMBO J. 17:74807489.
46. Inagaki, M.,, Y. Matsuoka,, K. Tsujimura,, S. Ando,, T. Tokui,, T. Takahashi,, and N. Inagaki. 1996. Dynamic property of intermediate filaments: regulation by phosphorylation. Bioessays 18:481487.
47. Irurzun, A.,, S. Sanchez-Palomino,, I. Novoa,, and L. Carrasco. 1995. Monensin and nigericin prevent the inhibition of host translation by poliovirus, without affecting p220 cleavage. J. Virol. 69:74537460.
48. Jackson, R. J.,, and M. Wickens. 1997. Translational controls impinging on the 5'-untranslated region and initiation factor proteins. Curr. Opin. Genet. Dev. 7:233241.
49. Jaramillo, M.,, T. E. Dever,, W. C. Merrick,, and N. Sonenberg. 1991. RNA unwinding in translation: assembly of helicase complex intermediates comprising eukaryotic initiation factors eIF-4F and eIF-4B. Moll. Cell. Biol. 11: 59925997.
50. Jewell, J. E.,, L. A. Ball,, and R. Rueckert. 1990. Limited expression of poliovirus by vaccinia virus recombinants due to inhibition of the vector by proteinase 2A. J. Virol. 64:13881393.
51. Johannes, G.,, M. S. Carter,, M. B. Eisen,, P. O. Brown,, and P. Sarnow. 1999. Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Proc. Natl. Acad. Sci. USA 96:1311813123.
52. Kim, J. L.,, K. A. Morgenstern,, C. Lin,, T. Fox,, M. D. Dwyer,, J. A. Landro,, S. P. Chambers,, W. Markland,, C. A. Lepre,, E. T. O'Malley,, S. L. Harberson,, C. M. Rice,, M. A. Murcko,, P. R. Caron,, and J. A. Thomson. 1996. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 87:343355.
53. Kirchweger, R.,, E. Ziegler,, B. J. Lamphear,, D. Waters,, H.-D. Liebig,, W. Sommergruber,, F. Sobrino,, C. Hohenadl,, D. Blaas,, R. E. Rhoads,, and T. Skern. 1994. Foot-and-mouth disease virus leader proteinase: purification of the Lb form and determination of its cleavage site on eIF-4γ. J. Virol. 68:56775684.
54. Kitamura, N.,, B. L. Semler,, P. G. Rothberg,, G. R. Larsen,, C. J. Adler,, A. J. Dorner,, E. A. Emini,, R. Hanecak,, J. J. Lee,, S. Van Der Werf,, C. W. Anderson,, and E. Wimmer. 1981. Primary structure, gene organization, polypeptide expression of poliovirus RNA, Nature 291: 547553.
55. Koenig, H.,, and B. Rosenwirth. 1988. Purification and partial characterization of poliovirus protease 2A by means of a functional assay. J. Virol. 62:12431250.
56. Kozak, M. 1978. How do eucaryotic ribosomes select initiation regions in messenger RNA? Cell 15:11091123.
57. Kozak, M. 1989. The scanning model for translation: an update. J. Cell Biol. 108:229241.
58. Kozak, M. 1997. Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6. EMBO J. 16:24822492.
59. Kräusslich, H. G.,, and E. Wimmer. 1988. Viral proteinases. Ann. Rev. Biochem. 57:701754.
60. Kräusslich, H.-G.,, M. J. H. Nickiin,, H. Toyoda,, D. Etchison,, and E. Wimmer. 1987. Poliovirus proteinase 2A induces cleavage of eukaryotic initiation factor 4F polypeptide p220. J. Virol. 61:27112718.
61. Lamphear, B. J.,, R. Kirchweger,, T. Skern,, and R. E. Rhoads. 1995. Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. J. Biol. Chem. 270:2197521983.
62. Lamphear, B. J.,, R. Yan,, F. Yang,, D. Waters,, H.-D. Liebig,, H. Klump,, E. Kuechler,, T. Skern,, and R. E. Rhoads. 1993. Mapping the cleavage site in protein synthesis initiation factor eIF-4γ of the 2A proteases from human coxsackievirus and rhinovirus. J. Biol. Chem. 268:1920019203.
63. Lee, C. K.,, and E. Wimmer. 1988. Proteolytic processing of poliovirus polyprotein: elimination of 2Apro-mediated, alternative cleavage of polypeptide 3CD by in vitro mutagenesis. Virology 166:405414.
64. Lee, K. A. W.,, I. Edery,, and N. Sonenberg. 1985. Isolation and structural characterization of cap-binding proteins from poliovirus-infected HeLa cells. J. Virol. 54: 515524.
65. Lee, K. A. W.,, I. Edery,, R. Hanecak,, E. Wimmer,, and N. Sonenberg. 1985. Poliovirus protease 3C (P3-7c) does not cleave p220 of eucaryotic mRNA cap-binding protein complex. J. Virol. 55:489493.
66. Lee, Y. F.,, A. Nomoto,, B. M. Detjen,, and E. Wimmer. 1977. A protein covalently linked to poliovirus genome RNA. Proc. Natl. Acad. Sci. USA 74:5963.
67. Liebig, H.-D.,, E. Ziegler,, R. Yan,, K. Hartmuth,, H. Klump,, H. Kowalski,, D. Blaas,, W. Sommergruber,, L. Frasel,, B. J. Lamphear,, R. E. Rhoads,, E. Kuechler,, and T. Skern. 1993. Purification of two picornaviral 2A proteinases: interaction with eIF-4γ and influence on in vitro translation. Biochemistry 32:75817588.
68. Lloyd, R. E.,, M. J. Grubman,, and E. Ehrenfeld. 1988. Relationship of p220 cleavage during Picornavirus infection to 2A proteinase sequencing. J. Virol. 62:42164223.
69. Lloyd, R. E.,, H. G. Jense,, and E. Ehrenfeld. 1987. Restriction of translation of capped mRNA in vitro as a model for poliovirus-induced inhibition of host cell protein synthesis: relationship to p220 cleavage. J. Virol. 61: 24802488.
70. Lloyd, R. E.,, H. Toyoda,, D. Etchison,, E. Wimmer,, and E. Ehrenfeld. 1986. Cleavage of the cap binding protein complex polypeptide p220 is not effected by the second poliovirus protease 2A. Virology 150:299303.
71. Lu, H. H.,, X. Li,, A. Cuconati,, and E. Wimmer. 1995. Analysis of Picornavirus 2A(pro) proteins: separation of proteinase from translation and replication functions. J. Virol. 69:74457452.
72. Luderer-Gmach, M.,, H.-D. Liebig,, W. Sommergruber,, T. Voss,, F. Fessl,, T. Skern,, and E. Kuechler. 1996. A human rhinovirus 2A proteinase mutant and its second site revertants. Biochem. J. 318:213218.
73. Mader, S.,, H. Lee,, A. Pause,, and N. Sonenberg. 1995. The translation initiation factor eIF4E binds to a common motif shared by the translation factor eIF-4γ and the translational repressors 4E-binding proteins. Mol. Cell. Biol. 15:49904997.
74. Medina, M.,, E. Domingo,, J. K. Brangwyn,, and G. J. Belsham. 1993. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology 194:355359.
75. Michel, Y. M.,, D. Poncet,, M. Piron,, M. K. Kean,, and A. M. Borman. 2000. Cap-poly(A) synergy in mammalian cell-free extracts: investigation of the requirements for poly(A)-mediated stimulation of translation initiation. J. Biol. Chem. 275:3226832276.
76. Molla, A.,, C. U. T. Hellen,, and E. Wimmer. 1993. Inhibition of proteolytic activity of poliovirus and rhinovirus 2A proteinases by elastase-specific inhibitors. J. Virol. 76:46884695.
77. Morley, S. J.,, P. S. Curtis,, and V. M. Pain. 1997. eIF4G: translation's mystery factor begins to yield its secrets. RNA 3:10851104.
78. Nickiin, M. J.,, H.-G. Kräusslich,, H. Toyoda,, J. J. Dunn,, and E. Wimmer. 1987. Poliovirus polypeptide precursors: expression in vitro and processing by exogenous 3C and 2A proteinases. Proc. Natl. Acad. Sci. USA 84:40024006.
79. Niepmann, M. 1999. Internal initiation of translation of picornaviruses, hepatitis C virus and pestiviruses. Recent Res. Devel. Virol. 1:229250.
80. Nomoto, A.,, Y. F. Lee,, and E. Wimmer. 1976. The 5'-end of poliovirus mRNA is not capped with m7G(5')ppp(5')Np. Proc. Natl. Acad. Sci. USA 73:375380.
81. Novoa, I.,, M. Cotton,, and L. Carrasco. 1996. Hybrid proteins between Pseudomonas aeruginosa exotoxin A and poliovirus 2Apro cleave p220 in HeLa cells. J. Virol. 70: 33193324.
82. Novoa, L.,, E. Feduchi,, and L. Carrasco. 1994. Hybrid proteins between Pseudomonas exotoxin A and poliovirus protease 2Apro. FEBS Lett. 355:4548.
83. Ohlmann, T.,, M. Rau,, V. M. Pain,, and S. J. Morley. 1996. The C-terminal domain of eukaryotic protein synthesis initiation factor (elF) 4G is sufficient to support cap-independent translation in the absence of elF4E. EMBO J. 15:13711382.
84. O'Neil, R. E.,, and V. R. Racaniello. 1989. Inhibition of translation in cells infected with a poliovirus 2Apro mutant correlates with phosphorylation of the alpha subunit of eucaryotic initiation factor 2. J. Virol. 63:50695075.
85. Perez, L.,, and L. Carrasco. 1992. Lack of correlation between p220 cleavage and the shutoff of host translation after poliovirus infection. Virology 189:178186.
86. Pestova, T. V.,, I. N. Shatsky,, and C. U. T. Hellen. 1996. Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preiinitiation complexes. Mol. Cell. Biol. 16:68706878.
87. Petersen, J. F. W.,, M. M. Cherney,, H.-D. Liebig,, T. Skern,, E. Kuechler,, and M. N. G. James. 1999. The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis. EMBO J. 18:54635475.
88. Racaniello, V. R.,, and D. Baltimore. 1981. Molecular cloning of poliovirus cDNA and determination of the complete nucleotide sequence of the viral genome. Proc. Natl. Acad. Sci. USA 78:48874891.
89. Rau, M.,, T. Ohlmann,, S. J. Morley,, and V. M. Pain. 1996. A reevaluation of the cap-binding protein, eIF4E, as a rate-limiting factor for initiation of translation in reticulocyte lysate. J. Biol. Chem. 271:89838990.
90. Ray, B. K.,, T. G. Lawson,, J. C. Kramer,, M. H. Cladaras,, J. A. Grifo,, R. D. Abramson,, W. C. Merrick,, and R. E. Thach. 1985. ATP-dependent unwinding of messenger RNA structure by eukaryotic initiation factors. J. Biol. Chem. 260:76517658.
91. Roberts, L. O.,, R. A. Seamons,, and G. J. Belsham. 1998. Recognition of Picornavirus internal ribosome entry sites within cells; influence of cellular and viral proteins. RNA 4:520529.
92. Rothberg, P. G.,, T. J. R. Harris,, A. Nomoto,, and E. Wimmer. 1978. The genome-linked protein of picornaviruses. V. 04-(5'-uridinyl)-tyrosine is the bond between the genome-linked protein and the RNA of poliovirus. Proc. Natl. Acad. Sci. USA 75:48684872.
93. Rozen, F.,, I. Edery,, K. Meerovitch,, T. E. Dever,, W. C. Merrick,, and N. Sonenberg. 1990. Bidirectional RNA helicase activity of eukaryotic translation factors 4A and 4F. Mol. Cell. Biol. 10:11341144.
94. Ryan, M. D.,, A. M. Q. King,, and G. P. Thomas. 1991. Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence. J. Gen. Virol. 72:27272732.
95. Sachs, A. B.,, P. Sarnow,, and M. W. Hentze. 1997. Starting at the beginning, middle, and end: translation initiation in eukaryotes. Cell 89:831838.
96. Schechter, I.,, and A. Berger. 1967. On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 27:157162.
97. Seipelt, J.,, A. Guarne,, E. Bergmann,, M. James,, W. Sommergruber,, I. Fita,, and T. Skern. 1999. The structures of picornaviral proteinases. Virus Res. 62:159168.
98. Seipelt, J.,, H.-D. Liebig,, W. Sommergruber,, C. Gerner,, and E. Kuechler. 2000. 2A proteinase of human rhino-virus cleaves cytokeratin 8 in infected HeLa cells. J. Biol. Chem. 275:2008420089.
99. Skern, T., 1998. Picornain 2A, p. 713715. In A. J. Barrett,, N. D. Rawlings,, and J. F. Woessner (ed.), Handbook of Proteolytic Enzymes. Academic Press, London, United Kingdom.
100. Skern, T.,, W. Sommergruber,, H. Auer,, P. Volkmann,, M. Zorn,, H.-D. Liebig,, F. Fessl,, D. Blaas,, and E. Kuechler. 1991. Substrate requirements of a human rhinoviral 2A proteinase. Virology 181:4654.
101. Skern, T.,, W. Sommergruber,, D. Blaas,, P. Gruendler,, F. Fraundorfer,, C. Pieler,, I. Fogy,, and E. Kuechler. 1985. Human rhinovirus 2: complete nucleotide sequence and proteolytic processing signals in the capsid protein region. Nuckic Acids Res. 13:21112126.
102. Sommergruber, W.,, H. Ahorn,, H. Klump,, A. Zoephel,, F. Fessl,, D. Blaas,, E. Kuechler,, H.-D. Liebig,, and T. Skern. 1994- 2A proteinases of Coxsackie- and rhinovirus cleave peptides derived from eIF-4T via a common recognition motif. Virology 198:741745.
103. Sommergruber, W.,, H. Ahorn,, A. Zoephel,, I. Maurer-Fogy,, F. Fessl,, G. Schnorrenberg,, H.-D. Liebig,, D. Blaas,, E. Kuechler,, and T. Skern. 1992. Cleavage specificity on synthetic peptide substrates of human rhino-virus 2 proteinase 2A. J. Biol. Chem. 267:2263922644.
104. Sommergruber, W.,, G. Casari,, F. Fessl,, J. Seipelt,, and T. Skern. 1994. The 2A proteinase of human rhinovirus is a zinc containing enzyme. Virology 204:815818.
105. Sommergruber, W.,, J. Seipelt,, F. Fessl,, T. Skern,, H.-D. Liebig,, and G. Casari. 1997. Mutational analyses support a model for the HRV2 2A proteinase. Virology 234:203214.
106. Sommergruber, W.,, M. Zorn,, D. Blaas,, F. Fessl,, P. Volkmann,, I. Maurer-Fogy,, P. Pallai,, V. Merluzzi,, M. Matteo,, T. Skern,, and E. Kuechler. 1989. Polypeptide 2A of human rhinovirus type 2: identification as a protease and characterisation by mutational analysis. Virology 169:6877.
107. Sonenberg, N. 1990. Poliovirus translation. Curr. Top. Microbiol. Immunol. 161:2347.
108. Sonenberg, N., 1996. mRNA 5'cap-binding protein eIF4E and control of cell growth, p. 245269. In J. W. B. Hershey,, M. B. Mathews,, and N. Sonenberg (ed.), Translational Control. Cold Spring Harbor Laboratory Press, Plainview, N.Y.
109. Sonenberg, N.,, M. A. Morgan,, W. C. Merrick,, and A. J. Shatkin. 1978. A polypeptide in eukaryotic initiation factors that crosslinks specifically to the 5'-terminal cap in mRNA. Proc. Natl. Acad. Sci. USA 75:48434847.
110. Steinbock, F. A.,, B. Nikolic,, P. A. Coulombe,, E. Fuchs,, P. Traub,, and G. Wiche. 2000. Dose-dependent linkage, assembly inhibition and disassembly of vimentin and cytokeratin 5/14 filaments through plectin's intermediate filament-binding domain. J. Cell Sci. 113:483491.
111. Sun, X.-H.,, and D. Baltimore. 1989. Human immune-deficiency virus tat-regulated expression of poliovirus protein 2A inhibits mRNA translation. Proc. Natl. Acad. Sci. USA 86:21432146.
112. Svitkin, Y. V.,, A. Gradi,, H. Imataka,, S. Morino,, and N. Sonenberg. 1999. eIF4GII, but not eIF4GI, cleavage correlates with the inhibition of host cell protein synthesis after human rhinovirus infection. J. Virol. 73: 34673472.
113. Tarun, S. Z.,, and A. B. Sachs. 1996. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EMBO J. 15:71687177.
114. Toyoda, H.,, M. J. H. Nickiin,, M. G. Murray,, C. W. Anderson,, J. J. Dunn,, F. W. Studier,, and E. Wimmer. 1986. A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein. Cell 45: 761770.
115. Ventoso, I.,, A. Barco,, and L. Carrasco. 1998. Mutational analysis of poliovirus 2Apro. Distinct inhibitory functions of 2Apro on translation and transcription. J. Biol. Chem. 273:2796027970.
116. Ventoso, I.,, S. E. MacMillan,, J. W. Hershey,, and L. Carrasco. 1998. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 435: 7983.
117. Voss, T.,, R. Meyer,, and W. Sommergruber. 1995. Spectroscopic characterization of rhinoviral protease 2A: Zn is essential for the structural integrity. Protein Sci. 4: 25262531.
118. Wang, Q. M.,, R. B. Johnson,, W. Sommergruber,, and T. A. Shepherd. 1998. Development of in vitro peptide substrates for human rhinovirus-14 2A protease. Arch. Biochem. Biophys. 356:1218.
119. Wimmer, E. 1982. Genome-linked proteins of viruses. Cell 28:199201.
120. Wyckoff, E. E.,, J. W. B. Hershey,, and E. Ehrenfeld. 1990. Eucaryotic initiation factor 3 is required for poliovirus 2A protease-induced cleavage of the p220 component of eucaryotic initiation factor 4F. Proc. Natl. Acad. Sci. USA 87:95299533.
121. Wyckoff, E. E.,, R. E. Lloyd,, and E. Ehrenfeld. 1992. Relationship of eukaryotic initiation factor 3 to poliovirus-induced p220 cleavage activity. J. Virol. 66: 29432951.
122. Yu, S. F.,, and R. E. Lloyd. 1991. Identification of essential amino acid residues in the functional activity of poliovirus 2A protease. Virology 182:615625.
123. Yu, S. F.,, and R. E. Lloyd. 1992. Characterization of the roles of conserved cysteine and histidine residues in poliovirus 2A protease. Virology 186:725735.
124. 124Ziegler, E.,, A. M. Borman,, F. G. Deliat,, H.-D. Liebig,, D. Jugovic,, K. M. Kean,, T. Skern,, and E. Kuechler. 1995. Picornavirus 2A proteinase-mediated stimulation of internal initiation of translation is dependent on enzymatic activity and the cleavage products of cellular proteins. Virology 213:549557.
125. Ziegler, E.,, A. M. Borman,, R. Kirchweger,, T. Skern,, and K. M. Kean. 1995. Foot-and mouth disease virus Lb proteinase can stimulate rhinovirus and enterovirus IRES-driven translation and cleaves several proteins of cellular and viral origin. J. Virol. 69:34653474.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error