Deveraux Q L, Takahashi R, Salvesen G S, Reed J C
The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, California 92037, USA.
Nature. 1997 Jul 17;388(6639):300-4. doi: 10.1038/40901.
The inhibitor-of-apoptosis (IAP) family of genes has an evolutionarily conserved role in regulating programmed cell death in animals ranging from insects to humans. Ectopic expression of human IAP proteins can suppress cell death induced by a variety of stimuli, but the mechanism of this inhibition was previously unknown. Here we show that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. As the caspases are highly conserved throughout the animal kingdom and are the principal effectors of apoptosis, our findings suggest how IAPs might inhibit cell death, providing evidence for a mechanism of action for these mammalian cell-death suppressors.
凋亡抑制蛋白（IAP）基因家族在调控从昆虫到人类等动物的程序性细胞死亡过程中具有进化上保守的作用。人IAP蛋白的异位表达能够抑制多种刺激诱导的细胞死亡，但其抑制机制此前尚不清楚。在此我们表明，人类X染色体连锁的IAP直接抑制细胞死亡蛋白酶caspase家族的至少两个成员，即caspase-3和caspase-7。由于caspase在整个动物界高度保守且是凋亡的主要效应因子，我们的发现揭示了IAP可能抑制细胞死亡的方式，为这些哺乳动物细胞死亡抑制因子的作用机制提供了证据。
