Laboratory for Histogenetic Dynamics, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Genes Cells. 2012 Feb;17(2):83-97. doi: 10.1111/j.1365-2443.2011.01579.x.
The caspases, a family of cysteine proteases, function as central regulators of cell death. Recently, caspase activity and caspase substrates identified in the absence of cell death have sparked strong interest in caspase functions in nonapoptotic cellular responses; these functions suggest that caspases may be activated without inducing or before apoptosis, thus leading to the cleavage of a specific subset of substrates. This review focuses primarily on the caspase enzymatic activity. Detailed genetic analyses of caspase-deficient Caenorhabditis elegans, Drosophila, and mice have shown that caspases are essential, not only for controlling the number of cells involved in sculpting or deleting structures in developing animals, but also for dynamic, nonapoptotic cell processes, such as innate immune response, tissue regeneration, cell-fate determination, stem-cell differentiation and neural activation. Our understanding of the spatio-temporal caspase activation mechanisms has advanced, primarily through the study of Drosophila developmental processes. This review will discuss current findings regarding caspase functions in cytoskeletal modification, morphogenetic regulation of cell shape, cell migration and the production of mechanical force during embryogenesis.
半胱氨酸蛋白酶家族中的胱天蛋白酶作为细胞死亡的中央调控因子发挥作用。最近，在没有细胞死亡的情况下鉴定出的胱天蛋白酶活性和底物引起了人们对胱天蛋白酶在非细胞凋亡的细胞反应中的功能的强烈兴趣；这些功能表明胱天蛋白酶可能在不诱导或在凋亡之前被激活，从而导致特定亚组底物的切割。这篇综述主要集中在胱天蛋白酶的酶活性上。对缺乏 Caspase 的秀丽隐杆线虫、果蝇和小鼠的详细遗传分析表明，Caspase 不仅对控制参与塑造或删除发育动物结构的细胞数量是必需的，而且对动态的、非凋亡的细胞过程也是必需的，如先天免疫反应、组织再生、细胞命运决定、干细胞分化和神经激活。我们对半胱天冬酶激活机制的时空理解已经取得了进展，主要是通过研究果蝇的发育过程。这篇综述将讨论关于胱天蛋白酶在细胞骨架修饰、细胞形状的形态发生调节、细胞迁移以及胚胎发生过程中产生机械力方面的功能的最新发现。
