Sahara S, Aoto M, Eguchi Y, Imamoto N, Yoneda Y, Tsujimoto Y
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Nature. 1999 Sep 9;401(6749):168-73. doi: 10.1038/43678.
Apoptosis is defined by several unique morphological nuclear changes, such as chromatin condensation and nuclear fragmentation. These changes are triggered by the activation of a family of cysteine proteases called caspases, and caspase-activated DNase (CAD/DFF40) and lamin protease (caspase-6) have been implicated in some of these changes. CAD/DFF40 induces chromatin condensation in purified nuclei, but distinct caspase-activated factor(s) may be responsible for chromatin condensation. Here we use an in vitro system to identify a new nuclear factor, designated Acinus, which induces apoptotic chromatin condensation after cleavage by caspase-3 without inducing DNA fragmentation. Immunodepletion experiments showed that Acinus is essential for apoptotic chromatin condensation in vitro, and an antisense study revealed that Acinus is also important in the induction of apoptotic chromatin condensation in cells.
细胞凋亡由几种独特的核形态变化所定义,比如染色质凝聚和核碎裂。这些变化是由一类名为半胱天冬酶的半胱氨酸蛋白酶激活所触发的,并且半胱天冬酶激活的脱氧核糖核酸酶(CAD/DFF40)和核纤层蛋白酶(半胱天冬酶-6)与其中一些变化有关。CAD/DFF40在纯化的细胞核中诱导染色质凝聚,但不同的半胱天冬酶激活因子可能是染色质凝聚的原因。在此,我们使用体外系统鉴定出一种新的核因子,命名为Acinus,它在被半胱天冬酶-3切割后诱导凋亡性染色质凝聚,而不诱导DNA片段化。免疫去除实验表明,Acinus在体外对于凋亡性染色质凝聚至关重要,并且一项反义研究显示,Acinus在细胞中诱导凋亡性染色质凝聚方面也很重要。