颗粒酶M直接切割半胱天冬酶激活的脱氧核糖核酸酶（CAD）抑制剂，释放CAD，导致DNA片段化。
Granzyme M directly cleaves inhibitor of caspase-activated DNase (CAD) to unleash CAD leading to DNA fragmentation.
作者信息
Lu Hongxia, Hou Qiang, Zhao Tongbiao, Zhang Honglian, Zhang Qixiang, Wu Lianfeng, Fan Zusen
机构信息
National Laboratory of Biomacromolecules and Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China.
出版信息
J Immunol. 2006 Jul 15;177(2):1171-8. doi: 10.4049/jimmunol.177.2.1171.
Granzyme (Gzm)M is constitutively highly expressed in NK cells that may play a critical role in NK cell-mediated cytolysis. However, the function of GzmM has been less defined. Just one report showed GzmM induces a caspase-independent death pathway. In this study, we demonstrate a protein transfection reagent Pro-Ject can efficiently transport GzmM into target cells. GzmM initiates caspase-dependent apoptosis with typical apoptotic nuclear morphology. GzmM induces DNA fragmentation, not DNA nicking. GzmM can directly degrade inhibitor of caspase-activated DNase to release the nuclease activity of caspase-activated DNase for damaging DNA. Furthermore, GzmM cleaves the DNA damage sensor enzyme poly(ADP-ribose) polymerase to prevent cellular DNA repair and force apoptosis.
颗粒酶（Gzm）M在自然杀伤（NK）细胞中组成性高表达，这可能在NK细胞介导的细胞溶解中起关键作用。然而，GzmM的功能尚未完全明确。仅有一份报告显示GzmM可诱导一条不依赖半胱天冬酶的死亡途径。在本研究中，我们证明一种蛋白质转染试剂Pro-Ject能够有效地将GzmM转运到靶细胞中。GzmM通过典型的凋亡核形态引发依赖半胱天冬酶的凋亡。GzmM诱导DNA片段化，而非DNA切口。GzmM可直接降解半胱天冬酶激活的脱氧核糖核酸酶的抑制剂，以释放半胱天冬酶激活的脱氧核糖核酸酶的核酸酶活性来损伤DNA。此外，GzmM切割DNA损伤传感酶聚（ADP-核糖）聚合酶，以阻止细胞DNA修复并促使细胞凋亡。
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