Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded DNA nicks of target cells
Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded DNA nicks of target cells
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DOI：
10.1038/sj.cdd.4402040
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发表时间：
2007-03
影响因子：
12.4
通讯作者：
T. Zhao;Honglian Zhang;Yuting Guo;Qianjing Zhang;G. Hua;Hongxia Lu;Q. Hou;H. Liu;Z. Fan
中科院分区：
文献类型：
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作者：
T. Zhao;Honglian Zhang;Yuting Guo;Qianjing Zhang;G. Hua;Hongxia Lu;Q. Hou;H. Liu;Z. Fan
虽然颗粒酶（Gzms）A-和B-诱导的细胞死亡途径已经确定，很少有人知道其他孤儿Gzms如何在CTL介导的细胞毒性功能。GzmK和A是人类所有Gzms中的胰蛋白酶，它们在同一染色体上紧密连锁。在这项研究中，我们表明，GzmK可以有效地传递到靶细胞与阳离子脂质蛋白转染试剂Pro-Ject。我们发现人GzmK触发快速细胞死亡独立于半胱天冬酶激活。死亡的特征是磷脂酰丝氨酸的快速外化、核形态学变化和单链DNA缺口。GzmK以其重组和天然形式或在完整细胞中水解核小体组装蛋白SET。GzmK对SET的切割消除了其核小体组装活性。在GzmK加载后，SET和DNA酶NM 23 H1快速易位到细胞核中，SET被切割，其中NM 23 H1的核酸酶活性被激活以使染色体DNA产生切口。
Although granzymes (Gzms) A-and B-induced cell death pathways have been defined, little is known about how other orphan Gzms function in CTL-mediated cytotoxicity. GzmK and A are tryptases among all the Gzms of humans and they are closely linked on the same chromosome. In this study, we showed that GzmK can be efficiently delivered into target cells with a cationic lipid protein transfection reagent Pro-Ject. We found human GzmK triggers rapid cell death independently of caspase activation. The features of death are characterized by rapid externalization of phosphatidylserine, nuclear morphological changes and single-stranded DNA nicks. GzmK hydrolyzes the nucleosome assembly protein SET in its recombinant and native forms or in intact cells. Cleavage of SET by GzmK abrogates its nucleosome assembly activity. After GzmK loading, SET and DNase NM23H1 rapidly translocate into the nucleus and SET is cleaved, where the nuclease activity of NM23H1 is activated to nick chromosomal DNA.