Kutsyi M P, Kuznetsova E A, Gaziev A I
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142292, Russia.
Biochemistry (Mosc). 1999 Feb;64(2):115-26.
Genetically programmed (apoptotic) cell death plays a key role in cell and tissue homeostasis and in pathogenesis of various diseases. However, the mechanisms involved in apoptotic cell death are poorly understood. At present, the role of proteases in key events of apoptosis is intensively studied and discussed and the involvement of various proteolytic enzymes in the induction and development of the cell death is well-recognized. Proteases of various classes participating in apoptosis have been identified as well as some substrates of these proteases whose cleavage is critical to cell viability; specific protease inhibitors which prevent the cell death have been synthesized. This review summarizes new data on proteolytic enzymes involved in apoptosis and considers the mechanisms of activation of proteases upon induction of apoptosis and the pathways of their involvement in the cell death. The participation of nuclear proteolytic enzymes in the destabilization of chromatin structure and regulation of DNA fragmentation by endonucleases in apoptotic cells is discussed.
基因编程(凋亡)性细胞死亡在细胞和组织稳态以及各种疾病的发病机制中起着关键作用。然而,凋亡性细胞死亡所涉及的机制仍知之甚少。目前,蛋白酶在凋亡关键事件中的作用受到了深入研究和讨论,各种蛋白水解酶参与细胞死亡的诱导和发展已得到充分认识。已鉴定出参与凋亡的各类蛋白酶以及这些蛋白酶的一些底物,其切割对细胞活力至关重要;还合成了可防止细胞死亡的特异性蛋白酶抑制剂。本综述总结了有关参与凋亡的蛋白水解酶的新数据,并探讨了凋亡诱导时蛋白酶的激活机制及其参与细胞死亡的途径。还讨论了核蛋白水解酶在凋亡细胞中染色质结构不稳定以及核酸内切酶对DNA片段化调控中的作用。