The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein
The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein
复制标题
DOI：
10.1074/jbc.m303179200
复制
发表时间：
2003-10-03
影响因子：
4.8
通讯作者：
Alnemri, ES
中科院分区：
文献类型：
--
作者：
Hegde, R;Srinivasula, SM;Alnemri, ES
Smac/Diablo和HtrA 2/Omi是在细胞凋亡期间从人细胞线粒体释放的细胞凋亡（IAP）结合蛋白的抑制剂，并且通过从IAP抑制中释放半胱天冬酶来调节细胞凋亡。在这里，我们描述了一个蛋白水解加工的异构体的多肽链释放因子GSPT 1/eRF 3蛋白，其功能在翻译，作为一个新的IAP结合蛋白的鉴定。与其他IAP结合蛋白一样，经加工的GSPT 1蛋白具有保守的N-末端IAP结合基序（AKPF）。此外，处理GSPT 1与IAP发生生物化学相互作用，并可促进caspase活化、IAP泛素化和凋亡。这些活动绝对需要的IAP结合基序的处理GSPT 1。我们的研究结果是一致的模型，即GSPT 1的IAP结合亚型的处理可以通过释放半胱天冬酶IAP抑制，或目标IAP和处理GSPT 1的蛋白酶体介导的降解增强细胞凋亡。
Smac/Diablo and HtrA2/Omi are inhibitors of apoptosis (IAP)-binding proteins released from the mitochondria of human cells during apoptosis and regulate apoptosis by liberating caspases from IAP inhibition. Here we describe the identification of a proteolytically processed isoform of the polypeptide chain-releasing factor GSPT1/eRF3 protein, which functions in translation, as a new IAP-binding protein. In common with other IAP-binding proteins, the processed GSPT1 protein harbors a conserved N-terminal IAP-binding motif (AKPF). Additionally, processed GSPT1 interacts biochemically with IAPs and could promote caspase activation, IAP ubiquitination and apoptosis. The IAP-binding motif of the processed GSPT1 is absolutely required for these activities. Our findings are consistent with a model whereby processing of GSPT1 into the IAP-binding isoform could potentiate apoptosis by liberating caspases from IAP inhibition, or target IAPs and the processed GSPT1 for proteasome-mediated degradation.