Caspase-3 cleaves the expanded androgen receptor protein of spinal and bulbar muscular atrophy in a polyglutamine repeat length-dependent manner
Caspase-3 cleaves the expanded androgen receptor protein of spinal and bulbar muscular atrophy in a polyglutamine repeat length-dependent manner
复制标题
DOI：
10.1006/bbrc.1998.9624
复制
发表时间：
1998-11-09
影响因子：
3.1
通讯作者：
Sobue, G
中科院分区：
文献类型：
--
作者：
Kobayashi, Y;Miwa, S;Sobue, G
脊髓延髓肌萎缩症（SBMA）是一组由多聚谷氨酰胺扩增引起的人类遗传性神经退行性疾病之一。越来越多的证据表明，含有扩展的多聚谷氨酰胺道的截短蛋白的产生可能是这些疾病的发病机制中的重要步骤。我们以前已经证明，SBMA基因产物，雄激素受体（AR）蛋白，是有毒的截断时。我们现在报告，在体外翻译的全长AR蛋白含有不同大小的多聚谷氨酰胺重复序列（分别为24，65和97个重复序列）的重组半胱天冬酶-3特异性裂解，释放一个多聚谷氨酰胺含有片段，切割的敏感性是多聚谷氨酰胺重复序列长度依赖性。提示AR蛋白是caspase-3裂解的“死亡底物”之一，caspase-3可能参与SBMA的发病过程。(C)北京：科学出版社.
Spinal and bulbar muscular atrophy (SBMA) is one of a group of human inherited neurodegenerative diseases caused by polyglutamine expansion. There is increasing evidence that generation of truncated proteins containing an expanded polyglutamine tract may be an important step in the pathogenesis of these disorders. We have previously demonstrated that the SBMA gene product, the androgen receptor (AR) protein, is toxic when truncated. We now report that in vitro translated full-length AR proteins containing different sized polyglutamine repeats (24, 65 and 97 repeats, respectively) are specifically cleaved by recombinant caspase-3, liberating a polyglutamine containing fragment, and that the susceptibility to cleavage is polyglutamine repeat length-dependent. These findings suggest that AR protein is one of the "death substrates" cleaved by caspase-3 and that caspase-3 might be involved in the pathogenesis of SBMA. (C) 1998 Academic Press.