Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract
Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract
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DOI：
10.1038/ng0896-442
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发表时间：
1996-08-01
期刊：
影响因子：
30.8
通讯作者：
Hayden, MR
中科院分区：
文献类型：
--
作者：
Goldberg, YP;Nicholson, DW;Hayden, MR
细胞凋亡是亨廷顿病（HD）的一种细胞死亡方式。脱辅基蛋白酶是线虫半胱氨酸蛋白酶死亡基因产物CED-3的人类对应物，在导致细胞凋亡的蛋白水解事件中具有关键作用。在这里，我们表明，凋亡提取物和apopain本身特异性切割HD基因产物，亨廷顿蛋白。切割速率随着亨廷顿多聚谷氨酰胺束的长度而增加，这为与CAG扩增相关的功能获得提供了解释。我们的研究结果表明，亨廷顿蛋白是由半胱氨酸蛋白酶切割，并建议HD可能是一种不适当的凋亡紊乱。
Apoptosis has recently been recognized as a mode of cell death in Huntington disease (HD). Apopain, a human counterpart of the nematode cysteine protease death-gene product, CED-3, has a key role in proteolytic events leading to apoptosis. Here we show that apoptotic extracts and apopain itself specifically cleave the HD gene product, huntingtin. The rate of cleavage increases with the length of the huntingtin polyglutamine tract, providing an explanation for the gain-of-function associated with CAG expansion. Our results show that huntingtin is cleaved by cysteine proteases and suggest that HD might be a disorder of inappropriate apoptosis.