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
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
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DOI：
10.1074/jbc.m100384200
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发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
Clemens, MJ
中科院分区：
文献类型：
--
作者：
Bushell, M;Wood, W;Clemens, MJ
真核起始因子（eIF）4 B与起始途径的几种组分相互作用，并在细胞凋亡期间靶向裂解。在无细胞系统中，caspase-3对eIF 4 B的裂解与蛋白质合成活性的一般抑制相一致。亲和层析证明哺乳动物eIF 4 B与poly（A）结合蛋白相互作用，并且由eIF 4 B的N-末端80个氨基酸组成的区域对于这种结合是必要的和足够的。当eIF 4 B被半胱天冬酶-3切割时，这种相互作用丧失，半胱天冬酶-3去除了N末端的45个氨基酸。类似地，当细胞被诱导经历凋亡时，eIF 4 B与poly（a）结合蛋白在体内的结合减少。使用人鼻病毒3C蛋白酶切割poly（A）结合蛋白本身也消除了与eIF 4 B的相互作用。因此，哺乳动物eIF 4 B和poly（A）结合蛋白之间的结合的破坏可以在细胞凋亡和小核糖核酸病毒感染期间发生，并且可能有助于在这些条件下观察到的翻译抑制。
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.