Hsu S-L, Yu C-T R, Yin S-C, Tang M-J, Tien A-C, Wu Y-M, Huang C-Y F
Department of Education and Research, Taichung Veterans General Hospital, Taichung 407, Taiwan, ROC.
Apoptosis. 2006 May;11(5):765-71. doi: 10.1007/s10495-006-5880-x.
Caspases have been known for several years for their involvement in executing apoptosis, where unwanted or damaged cells are eliminated. Surprisingly, after analysis of the relevant data set from the Stanford microarray database, we noticed that the gene expression pattern for caspase 3, but not for caspase 1, 6, 7, 8, 9, or 10, undergoes periodic change in the HeLa cell cycle. In this study, we have demonstrated that caspase 3, but not other caspases, is upregulated and activated just prior to mitosis. Pretreatment of human hepatoma cells with a caspase 3 inhibitor z-DEVD-FMK, prior to the treatment with an antimicrotubule drug nocodazole, abrogates the mitotic arrest, suggesting that caspase 3 (or a caspase 3-like enzyme) might be involved in mitotic-spindle checkpoint. The studies not only characterize caspase 3 as a cell cycle-regulated protein, but also link the protein to nocodazole-dependent mitotic checkpoint, greatly expanding the understanding of caspase 3.
多年来,人们一直知道半胱天冬酶参与执行细胞凋亡过程,即清除不需要或受损的细胞。令人惊讶的是,在分析来自斯坦福微阵列数据库的相关数据集后,我们注意到半胱天冬酶3的基因表达模式在HeLa细胞周期中呈周期性变化,而半胱天冬酶1、6、7、8、9或10的基因表达模式则没有。在本研究中,我们证明了只有半胱天冬酶3,而非其他半胱天冬酶,在有丝分裂前被上调并激活。在用抗微管药物诺考达唑处理之前,用人肝癌细胞与半胱天冬酶3抑制剂z-DEVD-FMK进行预处理,可消除有丝分裂停滞,这表明半胱天冬酶3(或一种类似半胱天冬酶3的酶)可能参与有丝分裂纺锤体检查点。这些研究不仅将半胱天冬酶3表征为一种细胞周期调节蛋白,还将该蛋白与诺考达唑依赖性有丝分裂检查点联系起来,极大地扩展了对半胱天冬酶3的理解。