Disruption of the interaction of mammalian protein synthesis eukaryotic initiation factor 4B with the poly(A)-binding protein by caspase- and viral protease-mediated cleavages.
Eukaryotic initiation factor (eIF) 4B interacts with several components of the initiation pathway and is targeted for cleavage during apoptosis. In a cell-free system, cleavage of eIF4B by caspase-3 coincides with a general inhibition of protein synthetic activity. Affinity chromatography demonstrates that mammalian eIF4B interacts with the poly(A)-binding protein and that a region consisting of the N-terminal 80 amino acids of eIF4B is both necessary and sufficient for such binding. This interaction is lost when eIF4B is cleaved by caspase-3, which removes the N-terminal 45 amino acids. Similarly, the association of eIF4B with the poly(A)-binding protein in vivo is reduced when cells are induced to undergo apoptosis. Cleavage of the poly(A)-binding protein itself, using human rhinovirus 3C protease, also eliminates the interaction with eIF4B. Thus, disruption of the association between mammalian eIF4B and the poly(A)-binding protein can occur during both apoptosis and picornaviral infection and is likely to contribute to the inhibition of translation observed under these conditions.
Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom.
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M
Bushell
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Wood
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Carpenter
V M
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Pain
S J
SJ
Morley
M J
MJ
Clemens
D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D039642:Eukaryotic Initiation Factors; D006801:Humans; D019169:Jurkat Cells; D008954:Models, Biological; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010850:Picornaviridae Infections / Q000378:metabolism; D039102:Poly(A)-Binding Proteins; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
D039642:Eukaryotic Initiation Factors; D010448:Peptide Initiation Factors; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D014764:Viral Proteins; C031799:eIF-4B; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases