Glas R, Bogyo M, McMaster J S, Gaczynska M, Ploegh H L
Center for Cancer Research, Department for Biology, Massachusetts Institute of Technology, Cambridge 02139-4307, USA.
Nature. 1998 Apr 9;392(6676):618-22. doi: 10.1038/33443.
Proteolysis is essential for the execution of many cellular functions. These include removal of incorrectly folded or damaged proteins, the activation of transcription factors, the ordered degradation of proteins involved in cell cycle control, and the generation of peptides destined for presentation by class I molecules of the major histocompatibility complex. A multisubunit protease complex, the proteasome, accomplishes these tasks. Here we show that in mammalian cells inactivation of the proteasome by covalent inhibitors allows the outgrowth of inhibitor-resistant cells. The growth of such adapted cells is apparently maintained by the induction of other proteolytic systems that compensate for the loss of proteasomal activity.
蛋白质水解对于许多细胞功能的执行至关重要。这些功能包括去除错误折叠或受损的蛋白质、激活转录因子、有序降解参与细胞周期调控的蛋白质，以及生成由主要组织相容性复合体I类分子呈递的肽段。一种多亚基蛋白酶复合体，即蛋白酶体，完成这些任务。我们在此表明，在哺乳动物细胞中，共价抑制剂使蛋白酶体失活会导致抗抑制剂细胞的生长。这种适应性细胞的生长显然是由其他蛋白水解系统的诱导来维持的，这些系统可补偿蛋白酶体活性的丧失。
