Drexler H C
Max Planck Institut für Physiologische und Klinische Forschung, Parkstr. 1, 61231 Bad Nauheim Germany.
Apoptosis. 1998;3(1):1-7. doi: 10.1023/a:1009604900979.
A characteristic feature of apoptotic cell death is the activation of a cascade of cytoplasmic proteases that results in the cleavage of a limited number of target proteins. A central role in these proteolytic events has been assigned to members of the capase family. However, the use of low molecular weight proteasomal inhibitors has also demonstrated that protein degradation or processing by the ubiquitin-proteasome system of the cell has a decisive impact on cell survival and death as well, depending on the cell type and/or the proliferative status of the cells studied. Treatment of proliferating cells with proteasome inhibitors leads to cell death, potentially involving an internal signalling conflict between accumulating levels of the cdk inhibitor p27Kip1 and c-myc. In contrast, in terminally differentiated cells the same compounds have the opposite effect of blocking apoptosis, possibly by preventing proteasome-mediated degradation of a capase inhibitor. In this review the role of proteasome-mediated proteolysis in the dying cell is discussed and apparently conflicting results are integrated into a working hypothesis which functionally locates the proteasome upstream of capase3-like enzymes.
凋亡性细胞死亡的一个特征是一系列细胞质蛋白酶的激活，这会导致有限数量的靶蛋白被切割。半胱天冬酶家族成员在这些蛋白水解事件中发挥着核心作用。然而，使用低分子量蛋白酶体抑制剂也已证明，细胞的泛素-蛋白酶体系统对蛋白质的降解或加工，同样会对细胞存活和死亡产生决定性影响，这取决于所研究细胞的类型和/或增殖状态。用蛋白酶体抑制剂处理增殖细胞会导致细胞死亡，这可能涉及细胞周期蛋白依赖性激酶抑制剂p27Kip1和c-myc积累水平之间的内部信号冲突。相反，在终末分化细胞中，相同的化合物具有相反的作用，即通过阻止蛋白酶体介导的半胱天冬酶抑制剂降解来阻断凋亡。在这篇综述中，我们讨论了蛋白酶体介导的蛋白水解在垂死细胞中的作用，并将明显相互矛盾的结果整合到一个工作假说中，该假说在功能上将蛋白酶体定位在类半胱天冬酶3酶的上游。
