Department of Biology, National University of Ireland, Maynooth, Co, Kildare, Ireland.
Cytotechnology. 1998 Sep;27(1-3):309-20. doi: 10.1023/A:1008014215581.
Recent developments in the apoptosis field have uncovered a family of cysteine proteases, the Caspases, that act as signalling components as well as effectors of the cell death machinery. Caspases are constitutively present as inactive precursors within most cells and undergo proteolytic processing in response to diverse death-inducing stimuli to initiate the death programme. Active caspases can process other caspases of the same type as well as process caspases further downstream in the pathway that ultimately leads to collapse of the cell. This cellular collapse is thought to occur as a consequence of caspase-mediated cleavage of a diverse array of cellular substrates. Regulation of entry into the death programme is controlled at a number of levels by members of the Bcl-2 family, as well as by other cell death regulatory proteins. Recent data has shed light upon the mechanism of action of these regulatory molecules and suggests that the point of caspase activation is a major checkpoint in the cell death programme. Because many transformed cell populations possess derangements in cell death-regulatory genes, such as bcl-2, such cells frequently exhibit elevated resistance to cytotoxic chemotherapy. Thus, a deeper understanding of how apoptosis is normally regulated has therapeutic implications for disease states where the normal controls on the cell death machinery have been subverted.
凋亡领域的最新进展揭示了一组半胱氨酸蛋白酶家族，即胱天蛋白酶，它们既是细胞死亡机制的信号成分，也是效应物。胱天蛋白酶在大多数细胞中作为无活性的前体持续存在，并在响应各种诱导死亡的刺激时发生蛋白水解加工，从而启动死亡程序。活性胱天蛋白酶可以对同一类型的其他胱天蛋白酶进行加工，也可以对途径中进一步下游的胱天蛋白酶进行加工，最终导致细胞崩溃。细胞崩溃被认为是胱天蛋白酶介导的对细胞内各种底物的切割的结果。细胞进入死亡程序的调控在多个水平上受到 Bcl-2 家族成员以及其他细胞死亡调控蛋白的控制。最近的数据揭示了这些调控分子的作用机制，并表明胱天蛋白酶激活的关键点是细胞死亡程序中的一个主要检查点。由于许多转化细胞群体的细胞死亡调控基因（如 bcl-2）存在紊乱，这些细胞通常对细胞毒性化疗表现出更高的抗性。因此，对凋亡如何正常调控的深入了解对那些正常控制细胞死亡机制已经被颠覆的疾病状态具有治疗意义。
