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.
Bushell
M
M
Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom.
Wood
W
W
Carpenter
G
G
Pain
V M
VM
Morley
S J
SJ
Clemens
M J
MJ
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