A combinatorial approach defines specificities of members of the caspase family and granzyme B - Functional, relationships established for key mediators of apoptosis
A combinatorial approach defines specificities of members of the caspase family and granzyme B - Functional, relationships established for key mediators of apoptosis
复制标题
DOI：
10.1074/jbc.272.29.17907
复制
发表时间：
1997-07-18
影响因子：
4.8
通讯作者：
Nicholson, DW
中科院分区：
文献类型：
--
作者：
Thornberry, NA;Ranon, TA;Nicholson, DW
有证据表明，caspase(白细胞介素1β转换酶/CED-3)家族的成员半胱氨酸蛋白酶和细胞毒性淋巴细胞衍生丝氨酸蛋白酶颗粒酶B在哺乳动物细胞凋亡中起着重要作用。在这里，我们使用一种新的方法，使用位置扫描底物组合文库来严格定义它们的个体特异性。结果将这些酶分为三个不同的组，并表明其中几个具有多余的功能。Caspase2、3和7以及秀丽线虫CED-3(DEXD)的特异性表明，所有这些酶都在上睑脱垂的效应阶段发挥作用，使必要的动态平衡途径丧失能力。相反，caspase 6、8和9以及颗粒酶B((I/L/V)EXD)的最佳序列类似于效应器caspase酶原中的激活位点，与这些酶作为上游成分在放大死亡信号的蛋白水解级联中的作用一致。
There is compelling evidence that members of the caspase (interleukin-1 beta converting enzyme/CED-3) family of cysteine proteases and the cytotoxic lymphocyte-derived serine protease granzyme B play essential roles in mammalian apoptosis. Here we use a novel method employing a positional scanning substrate combinatorial library to rigorously define their individual specificities. The results divide these proteases into three distinct groups and suggest that several have redundant functions. The specificity of caspases 2, 3, and 7 and Caenorhabditis elegans CED-3 (DEXD) suggests that all of these enzymes function to incapacitate essential homeostatic pathways during the effector phase of apo ptosis. In contrast, the optimal sequence for caspases 6, 8, and 9 and granzyme B ((I/L/V)EXD) resembles activation sites in effector caspase proenzymes, consistent with a role for these enzymes as upstream components in a proteolytic cascade that amplifies the death signal.