A molecular view of cytotoxic T lymphocyte induced killing
A molecular view of cytotoxic T lymphocyte induced killing
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DOI：
10.1139/o05-146
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发表时间：
2005-12-01
影响因子：
2.9
通讯作者：
Bleackley, RC
中科院分区：
文献类型：
--
作者：
Bleackley, RC
细胞毒性 T 淋巴细胞 (CTL) 会寻找并消灭致病细胞，例如感染病毒的细胞。阿尔伯塔大学（阿尔伯塔州埃德蒙顿）的生物化学实验室研究这些效应器使用的分子机制，这篇综述主要涵盖该小组关于该主题的研究。那里的研究始于发现颗粒酶基因并认识到颗粒酶 B (GrB) 具有不寻常的底物特异性。天冬氨酸残基的切割为我们提供了半胱天冬酶（细胞凋亡的关键调节因子）是重要底物的线索。然而，现在很清楚线粒体在控制颗粒酶诱导的细胞凋亡中也很重要。由此发现 Bcl2 家族的促凋亡成员 Bid 也能被 GrB 激活。然后，Cleaved Bid 易位至线粒体，导致凋亡蛋白抑制剂拮抗剂的释放。介绍了我们对 CTL 杀伤分子基础的理解的演变。
Cytotoxic T lymphocytes (CTLs) search out and destroy pathogenic cells, such as those infected with viruses. The biochemistry laboratory at the University of Alberta (Edmonton, Alta.) studies the molecular mechanisms used by these effectors, and this review covers research on this topic primarily from this group. Research there began with the discovery of the granzyme genes and the realization that granzyme B (GrB) had an unusual substrate specificity. Cleavage at aspartate residues gave us the clue that caspases, key regulators of apoptosis, were important substrates. However, it is now clear that mitochondria are also important in controlling granzyme-induced apoptosis. This led to the discovery that the proapoptotic member of the Bcl2 family, Bid, is also activated by GrB. Cleaved Bid then translocates to the mitochondria, resulting in the release of antagonists of inhibitors of apoptosis proteins. The evolution of our understanding of the molecular basis of CTL killing is presented.