IAP-antagonists exhibit non-redundant modes of action through differential DIAP1 binding

التفاصيل البيبلوغرافية
العنوان: IAP-antagonists exhibit non-redundant modes of action through differential DIAP1 binding
المؤلفون: Hermann Steller, Tencho Tenev, Julie Agapite, Pascal Meier, Lakshmi Goyal, Anna Zachariou
المصدر: The EMBO journal. 22(24)
سنة النشر: 2003
مصطلحات موضوعية: Cell Survival, Apoptosis, Plasma protein binding, Inhibitor of apoptosis, General Biochemistry, Genetics and Molecular Biology, Cell Line, Inhibitor of Apoptosis Proteins, Animals, Drosophila Proteins, Binding site, Mode of action, Molecular Biology, Caspase, Binding Sites, General Immunology and Microbiology, biology, General Neuroscience, Intrinsic apoptosis, fungi, Zinc Fingers, Articles, XIAP, Cell biology, body regions, Drosophila melanogaster, Caspases, biology.protein, sense organs, Protein Binding
الوصف: The Drosophila inhibitor of apoptosis protein DIAP1 ensures cell viability by directly inhibiting caspases. In cells destined to die this IAP-mediated inhibition of caspases is overcome by IAP-antagonists. Genetic evidence indicates that IAP-antagonists are non-equivalent and function synergistically to promote apoptosis. Here we provide biochemical evidence for the non-equivalent mode of action of Reaper, Grim, Hid and Jafrac2. We find that these IAP-antagonists display differential and selective binding to specific DIAP1 BIR domains. Consistently, we show that each DIAP1 BIR region associates with distinct caspases. The differential DIAP1 BIR interaction seen both between initiator and effector caspases and within IAP-antagonist family members suggests that different IAP-antagonists inhibit distinct caspases from interacting with DIAP1. Surprisingly, we also find that the caspase-binding residues of XIAP predicted to be strictly conserved in caspase-binding IAPs, are absent in DIAP1. In contrast to XIAP, residues C-terminal to the DIAP1 BIR1 domain are indispensable for caspase association. Our studies on DIAP1 and caspases expose significant differences between DIAP1 and XIAP suggesting that DIAP1 and XIAP inhibit caspases in different ways.
تدمد: 0261-4189
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b42f16739692cbe7803bdf21d66a166
https://pubmed.ncbi.nlm.nih.gov/14657035
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....0b42f16739692cbe7803bdf21d66a166
قاعدة البيانات: OpenAIRE