Direct interaction of Smac with NADE promotes TRAIL-induced apoptosis.
Second mitochondria-derived activator of caspase (Smac) has been implicated in the activation of apoptosis in response to cell stress. We screened for Smac/DIABLO-binding protein for further understanding of Smac-mediated apoptosis. We identified NADE, previously known as p75NTR-associated cell death executor, as a Smac-binding protein. Smac-NADE interaction was mapped to the ... N-terminal region of Samc and the C-terminal region of NADE. Co-expression of NADE and Smac promotes TRAIL-induced apoptosis in MCF-7 cells. Interestingly, the co-presence of Smac and NADE inhibits XIAP-mediated Smac ubiquitination. In conclusion, our results provide the first evidence that the interaction between Smac and NADE regulates apoptosis through the inhibition of Smac ubiquitination.
Mesh Terms:
Apoptosis, Apoptosis Regulatory Proteins, Carrier Proteins, Cell Line, Humans, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Mitochondrial Proteins, Protein Binding, Proteins, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha, Two-Hybrid System Techniques, X-Linked Inhibitor of Apoptosis Protein
Apoptosis, Apoptosis Regulatory Proteins, Carrier Proteins, Cell Line, Humans, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Mitochondrial Proteins, Protein Binding, Proteins, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha, Two-Hybrid System Techniques, X-Linked Inhibitor of Apoptosis Protein
Biochem. Biophys. Res. Commun.
Date: Jun. 25, 2004
PubMed ID: 15178455
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