Journal
CELL DEATH AND DIFFERENTIATION
Volume 7, Issue 7, Pages 628-636Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4400699
Keywords
apoptosis; BJAB cells; caspases; eIF4G; initiation factors; protein sequencing
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Polypeptide chain initiation factor elF4Gl undergoes caspase-mediated degradation during apoptosis to give characteristic fragments, The most prominent of these has an estimated mass of approximately 76 kDa (Middle-Fragment of Apoptotic cleavage of elF4G; M-FAG), Subcellular fractionation of the BJAB lymphoma cell line after induction of apoptosis indicates that M-FAG occurs in both ribosome-bound and soluble forms. Affinity chromatography on m(7)GTP-Sepharose shows that M-FAG retains the ability of elF4Gl to associate with both the mRNA cap-binding protein elF4E and initiation factor elF4A and that the ribosome-bound form of M-FAG is also present as a complex with elF4E and elF4A, These data suggest that the binding sites for elF4E, elF4A and elF3 on elF4Gl are retained in the caspase-generated fragment. M-FAG is also a substrate for cleavage by the Foot-and-Mouth-Disease Virus-encoded L protease, These properties, together with the pattern of recognition by a panel of antibodies, define the origin of the apoptotic cleavage fragment. N-terminal sequencing of the products of caspase-3-mediated elF4Gl cleavage has identified the major cleavage sites,The pattern of elF4Gl degradation and the possible roles of the individual cleavage products in cells undergoing apoptosis are discussed.
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