Wright M E, Han D K, Hockenbery D M
Molecular and Cellular Biology Program, Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
FEBS Lett. 2000 Sep 8;481(1):13-8. doi: 10.1016/s0014-5793(00)01962-1.
Using a heterologous yeast expression assay, we show that inhibitor of apoptosis proteins (IAPs) suppress caspase-3-mediated cytotoxicity in the order of XIAP>c-IAP2>c-IAP1>survivin. The same ordering of IAP activities was demonstrated in mammalian cells expressing an auto-activating caspase-3. The relative anti-apoptotic activities of each IAP depended on the particular death stimulus. For IAP-expressing cells treated with camptothecin, survival correlated with their intrinsic anti-caspase-3 activity. However, c-IAP1-transfected cells were disproportionately resistant to tumor necrosis factor-alpha, suggesting that its anti-apoptotic activities extend beyond caspase-3 or -7 inhibition. Yeast-based caspase assays provide rapid, reliable information on specificity and activity of the IAPs and aid in identifying critical targets in mammalian apoptotic pathways.
利用异源酵母表达分析，我们发现凋亡抑制蛋白（IAPs）以XIAP>c-IAP2>c-IAP1>存活素的顺序抑制caspase-3介导的细胞毒性。在表达自激活caspase-3的哺乳动物细胞中也证明了IAP活性的相同排序。每种IAP的相对抗凋亡活性取决于特定的死亡刺激。对于用喜树碱处理的表达IAP的细胞，存活与其内在的抗caspase-3活性相关。然而，转染c-IAP1的细胞对肿瘤坏死因子-α具有不成比例的抗性，这表明其抗凋亡活性超出了对caspase-3或-7的抑制作用。基于酵母的caspase分析提供了关于IAPs特异性和活性的快速、可靠信息，并有助于确定哺乳动物凋亡途径中的关键靶点。
