Induction of Rapid Histone Degradation by the Cytotoxic T Lymphocyte Protease Granzyme A*
Induction of Rapid Histone Degradation by the Cytotoxic T Lymphocyte Protease Granzyme A*
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DOI：
10.1074/jbc.m005390200
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发表时间：
2001-02
期刊：
影响因子：
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通讯作者：
D. Zhang;M. Pasternack;P. Beresford;L. Wagner;A. Greenberg;J. Lieberman
中科院分区：
文献类型：
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作者：
D. Zhang;M. Pasternack;P. Beresford;L. Wagner;A. Greenberg;J. Lieberman
细胞毒性 T 淋巴细胞蛋白酶颗粒酶 A 诱导不依赖 caspase 的细胞死亡，其中观察到 DNA 单链切口而不是寡核小体断裂。颗粒酶 A 是一种特异性类胰蛋白酶，集中在靶细胞的细胞核中，协同增强 caspase 激活剂颗粒酶 B 诱导的 DNA 片段化。在这里，我们表明，颗粒酶 A 处理分离的细胞核可增强 DNA 与外源核酸内切酶的可及性。在体外和细胞加载穿孔素后，GrnA 完全降解组蛋白 H1，并将核心组蛋白裂解为 ∼16-kDa 片段。组蛋白消化提供了一种在 T 细胞和自然杀伤细胞颗粒介导的细胞凋亡过程中展开压缩染色质并促进内源 DNase 接触 DNA 的机制。
The cytotoxic T lymphocyte protease granzyme A induces caspase-independent cell death in which DNA single-strand nicking is observed instead of oligonucleosomal fragmentation. Granzyme A is a specific tryptase that concentrates in the nucleus of targeted cells and synergistically enhances DNA fragmentation induced by the caspase activator granzyme B. Here we show that granzyme A treatment of isolated nuclei enhances DNA accessibility to exogenous endonucleases.In vitro and after cell loading with perforin, GrnA completely degrades histone H1 and cleaves core histones into ∼16-kDa fragments. Histone digestion provides a mechanism for unfolding compacted chromatin and facilitating endogenous DNase access to DNA during T cell and natural killer cell granule-mediated apoptosis.