Abstract
Survivin is a member of the inhibitor of apoptosis protein (IAP) family that has been implicated in both apoptosis inhibition and cell cycle control. However, its inhibitory mechanism and subcellular localization remain controversial. In this report, we provided evidence for the first time that Survivin physically interacts with Smac/DIABLO both in vitro and in vivo. A point mutation (D71R) in the baculovirus IAP repeat motif and a C-terminal deletion mutant (Surv-BIR) of Survivin fail to bind to Smac/DIABLO and abrogate its ability to inhibit apoptosis. The N-terminal of mature Smac/DIABLO is absolutely required for Survivin.Smac complex formation. Subcellular distributions of Survivin and Smac/DIABLO showed that they co-localized within the cytosol during interphase. In addition, Survivin was found to be incapable of binding to caspase. We also identified that the co-presence of Smac/DIABLO and XIAP was required for Survivin to inhibit caspase cleavage in a cell-free system. In conclusion, our results provide the first evidence that the interaction between Smac/DIABLO and Survivin is an essential step underling the inhibition of apoptosis induced by Taxol.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Antigens, Neoplasm / pharmacology
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins
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Binding Sites
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Carrier Proteins / physiology*
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Cell Cycle / physiology
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HeLa Cells
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Humans
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / physiology*
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Mitochondria / physiology
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Mitochondrial Proteins / physiology*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Neoplasm Proteins
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Paclitaxel / pharmacology*
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Point Mutation
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Polymerase Chain Reaction
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Recombinant Fusion Proteins / pharmacology
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Recombinant Proteins / pharmacology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Survivin
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Transfection
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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Apoptosis Regulatory Proteins
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BIRC5 protein, human
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Carrier Proteins
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DIABLO protein, human
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins
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Microtubule-Associated Proteins
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Mitochondrial Proteins
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Neoplasm Proteins
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Recombinant Fusion Proteins
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Recombinant Proteins
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Survivin
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Paclitaxel