Cleavage of 14-3-3 protein by caspase-3 facilitates bad interaction with Bcl-x(L) during apoptosis
Cleavage of 14-3-3 protein by caspase-3 facilitates bad interaction with Bcl-x(L) during apoptosis
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DOI：
10.1074/jbc.m213098200
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发表时间：
2003-05-23
影响因子：
4.8
通讯作者：
Joe, CO
中科院分区：
文献类型：
--
作者：
Won, J;Kim, DY;Joe, CO
14-3-3epsilon 蛋白被改良酵母双杂交系统鉴定为 caspase-3 底物之一。在培养的哺乳动物细胞中，细胞 14-3-3ε 蛋白也会因凋亡诱导剂的处理而被裂解。 14-3-3ε蛋白的Asp(238)被确定为caspase-3切割的位点。切割的14-3-3突变蛋白(D238)与Bad(一种促死亡Bcl-2家族蛋白)的亲和力低于野生型或不可切割的突变体14-3-3ε蛋白(D238A)。然而，在共表达 Bad 与截短形式的 14-3-3epsilon 蛋白 (D238) 的人 293T 细胞中，Bad 与细胞 Bcl-x(L) 的关联比在共表达 Bad 与野生型或不可切割的突变体 14-3-3epsilon 蛋白 (D238A) 的对照细胞中更有效。本研究表明，细胞凋亡过程中 14-3-3 蛋白的裂解通过从 14-3-3 蛋白中释放相关的 Bad 来促进细胞死亡，并促进 Bad 易位至线粒体及其与 Bcl-x(L) 的相互作用。
The 14-3-3epsilon protein was identified as one of the caspase-3 substrates by the modified yeast two-hybrid system. The cellular 14-3-3epsilon protein was also cleaved in response to the treatment of apoptosis inducers in cultured mammalian cells. Asp(238) of the 14-3-3epsilon protein was determined as the site of cleavage by caspase-3. The affinity of the cleaved 14-3-3 mutant protein (D238) to Bad, a death-promoting Bcl-2 family protein, was lower than that of wild type or the uncleavable mutant 14-3-3epsilon protein (D238A). However, Bad associated with the cellular Bcl-x(L) more effectively in human 293T cells coexpressing Bad with the truncated form of the 14-3-3epsilon protein ( D238) than in control cells co-expressing Bad with wild type or the uncleavable mutant 14-3-3epsilon protein ( D238A). The present study suggests that the cleavage of 14-3-3 protein during apoptosis promotes cell death by releasing the associated Bad from the 14-3-3 protein and facilitates Bad translocation to the mitochondria and its interaction with Bcl-x(L).