Caspase‐3 and inhibitor of apoptosis protein(s) interactions in Saccharomyces cerevisiae and mammalian cells

FEBS Letters

Han, David K¹  Wright, Michael E²  Hockenbery, David M² 

[1] Department of Molecular Biotechnology, University of Washington, Seattle, WA, USA;Molecular and Cellular Biology Program, Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA

关键词: Caspase;    Inhibitor of apoptosis protein;    Apoptosis;    Yeast;    GAL;    galactose;    HEK;    human embryonic kidney;    IAP;    inhibitor of apoptosis protein;    RCF;    relative colony frequency;    Rev-caspase-3;    reversed caspase-3;    TNF;    tumor necrosis factor;   

DOI  :  10.1016/S0014-5793(00)01962-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-α, 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.

【 授权许可】

Unknown