1. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity.
- Author
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Liston P, Fong WG, Kelly NL, Toji S, Miyazaki T, Conte D, Tamai K, Craig CG, McBurney MW, and Korneluk RG
- Subjects
- Adaptor Proteins, Signal Transducing, Adenoviridae genetics, Adenoviridae metabolism, Animals, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis genetics, Apoptosis physiology, Apoptosis Regulatory Proteins, Blotting, Northern, Blotting, Western, Caspase Inhibitors, Cell Survival, Culture Media, Serum-Free, Etoposide pharmacology, Genes, Reporter, Humans, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Neoplasm Proteins genetics, Plasmids genetics, Plasmids metabolism, Proteins genetics, Proteins metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Tumor Cells, Cultured, Two-Hybrid System Techniques, X-Linked Inhibitor of Apoptosis Protein, Zinc Fingers, Caspases metabolism, Enzyme Inhibitors metabolism, Neoplasm Proteins metabolism, Proteins antagonists & inhibitors
- Abstract
The inhibitors of apoptosis (IAPs) suppress apoptosis through the inhibition of the caspase cascade and thus are key proteins in the control of cell death. Here we have isolated the protein XIAP-associated factor 1 (XAF1) on the basis of its ability to bind XIAP, a member of the IAP family. XIAP suppresses caspase activation and cell death in vitro, and XAF1 antagonizes these XIAP activities. Expression of XAF1 triggers a redistribution of XIAP from the cytosol to the nucleus. XAF1 is ubiquitously expressed in normal tissues, but is present at low or undetectable levels in many different cancer cell lines. Loss of control over apoptotic signalling is now recognized as a critical event in the development of cancer. Our results indicate that XAF1 may be important in mediating the apoptosis resistance of cancer cells.
- Published
- 2001
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