DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis
DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis
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DOI：
10.1016/s1074-7613(00)80213-7
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发表时间：
2000-06-01
期刊：
影响因子：
32.4
通讯作者：
Ley, TJ
中科院分区：
文献类型：
--
作者：
Thomas, DA;Du, CY;Ley, TJ
颗粒酶B(GzmB)是细胞毒性淋巴细胞颗粒中的一种成分，能迅速启动靶细胞的凋亡。虽然一些原天冬氨酸酶被GzmB裂解并激活，但GzmB诱导的细胞凋亡对caspase激活的绝对要求是有争议的。在这篇报道中，我们证明了GzmB可以在caspase-3活性缺失的情况下通过直接切割DFF45/ICAD来释放激活的DFF40/CAD来启动细胞凋亡。在缺乏caspase-3活性的细胞中，DFF45/ICAD的切割效率较低，这表明caspase通常会放大GzmB死亡信号。DFF45/ICAD基因缺陷的小鼠胚胎成纤维细胞对GzmB诱导的死亡具有部分抵抗力，表明DFF45/ICAD在GzmB诱导的细胞凋亡中具有重要的生物学意义。
Granzyme B (GzmB) is a component of cytotoxic lymphocyte granules that can rapidly initiate apoptosis in target cells. While several procaspases are cleaved and activated by GzmB, the absolute requirement of caspase activation for GzmB-induced apoptosis is controversial. In this report, we demonstrate that GzmB can initiate apoptosis in the absence of caspase-3 activity by directly cleaving DFF45/ICAD to liberate activated DFF40/CAD. DFF45/ICAD cleavage occurs less efficiently in cells that lack caspase-3 activity, suggesting that the caspases normally amplify the GzmB death signal. DFF45/ICAD-deficient mouse embryo fibroblasts are partially resistant to GzmB-induced death, demonstrating the biological importance of DFF45/ICAD for GzmB-mediated apoptosis.