Bushell M, Wood W, Carpenter G, Pain V M, Morley S J, Clemens M J
Department of Biochemistry and Immunology, Cellular and Molecular Sciences Group, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom.
J Biol Chem. 2001 Jun 29;276(26):23922-8. doi: 10.1074/jbc.M100384200. Epub 2001 Mar 23.
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.
真核生物起始因子（eIF）4B与起始途径的多个组分相互作用，并且在细胞凋亡过程中会被切割。在无细胞体系中，半胱天冬酶-3对eIF4B的切割与蛋白质合成活性的普遍抑制同时发生。亲和层析表明，哺乳动物eIF4B与聚腺苷酸结合蛋白相互作用，并且eIF4B N端80个氨基酸组成的区域对于这种结合既是必需的也是足够的。当eIF4B被半胱天冬酶-3切割（去除N端45个氨基酸）时，这种相互作用就会丧失。同样，当细胞被诱导发生凋亡时，eIF4B与聚腺苷酸结合蛋白在体内的结合也会减少。使用人鼻病毒3C蛋白酶切割聚腺苷酸结合蛋白本身，也会消除其与eIF4B的相互作用。因此，哺乳动物eIF4B与聚腺苷酸结合蛋白之间的结合破坏可发生在细胞凋亡和小RNA病毒感染过程中，并且很可能导致在这些条件下观察到的翻译抑制。
