Salvesen Guy S, Riedl Stefan J
Program on Apoptosis and Cell Death, Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Adv Exp Med Biol. 2008;615:13-23. doi: 10.1007/978-1-4020-6554-5_2.
The main effectors of apoptosis encompass proteases from the caspase family, which reside as latent precursors in most nucleated animal cells. The apoptotic caspases constitute a minimal two-step signaling pathway. The apical (initiator) caspases are activated within oligomeric signaling complexes in response to apoptotic stimuli. Their mechanism of activation probably results from proximity-induced clustering to the dimeric active forms. Once activated, the apical caspases directly activate the executioner (effector) caspases by limited proteolytic cleavage. The distinct activation mechanisms explain how an apoptotic stimulus is converted to proteolytic activity, and how this activity is amplified to allow for limited proteolysis of the dozens of protein substrates whose cleavage is required for efficient apoptosis.
细胞凋亡的主要效应分子包括半胱天冬酶家族的蛋白酶,它们以无活性前体的形式存在于大多数有核动物细胞中。凋亡半胱天冬酶构成了一个最少两步的信号通路。顶端(起始)半胱天冬酶在寡聚信号复合物中响应凋亡刺激而被激活。它们的激活机制可能是由于邻近诱导聚集形成二聚体活性形式。一旦被激活,顶端半胱天冬酶通过有限的蛋白水解切割直接激活执行(效应)半胱天冬酶。这种独特的激活机制解释了凋亡刺激如何转化为蛋白水解活性,以及这种活性如何被放大,从而允许对数十种蛋白质底物进行有限的蛋白水解,而这些底物的切割是有效细胞凋亡所必需的。