Duckett C S, Li F, Wang Y, Tomaselli K J, Thompson C B, Armstrong R C
Howard Hughes Medical Institute, and Department of Medicine, The University of Chicago, Illinois 60637, USA.
Mol Cell Biol. 1998 Jan;18(1):608-15. doi: 10.1128/MCB.18.1.608.
The gene encoding human IAP-like protein (hILP) is one of several mammalian genes with sequence homology to the baculovirus inhibitor-of-apoptosis protein (iap) genes. Here we show that hILP can block apoptosis induced by a variety of extracellular stimuli, including UV light, chemotoxic drugs, and activation of the tumor necrosis factor and Fas receptors. hILP also protected against cell death induced by members of the caspase family, cysteine proteases which are thought to be the principal effectors of apoptosis. hILP and Bcl-xL were compared for their ability to affect several steps in the apoptotic pathway. Redistribution of cytochrome c from mitochondria, an early event in apoptosis, was not blocked by overexpression of hILP but was inhibited by Bcl-xL. In contrast, hILP, but not Bcl-xL, inhibited apoptosis induced by microinjection of cytochrome c. These data suggest that while Bcl-xL may control mitochondrial integrity, hILP can function downstream of mitochondrial events to inhibit apoptosis.
编码人IAP样蛋白（hILP）的基因是与杆状病毒凋亡抑制蛋白（iap）基因具有序列同源性的几个哺乳动物基因之一。在此我们表明，hILP可阻断由多种细胞外刺激诱导的凋亡，这些刺激包括紫外线、化学毒性药物以及肿瘤坏死因子和Fas受体的激活。hILP还能保护细胞免受半胱天冬酶家族成员诱导的细胞死亡，半胱天冬酶是一类被认为是凋亡主要效应因子的半胱氨酸蛋白酶。比较了hILP和Bcl-xL影响凋亡途径中几个步骤的能力。细胞色素c从线粒体的重新分布是凋亡早期事件，hILP的过表达并未阻断此过程，但Bcl-xL可抑制。相反，hILP而非Bcl-xL可抑制细胞色素c显微注射诱导的凋亡。这些数据表明，虽然Bcl-xL可能控制线粒体完整性，但hILP可在线粒体事件的下游发挥作用以抑制凋亡。
