Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis / physiology*
-
Apoptosis Regulatory Proteins
-
Carrier Proteins / metabolism*
-
Cell Line
-
Humans
-
Intracellular Signaling Peptides and Proteins
-
Membrane Glycoproteins / metabolism
-
Membrane Glycoproteins / physiology*
-
Mitochondrial Proteins / metabolism*
-
Protein Binding
-
Proteins / metabolism*
-
TNF-Related Apoptosis-Inducing Ligand
-
Tumor Necrosis Factor-alpha / metabolism
-
Tumor Necrosis Factor-alpha / physiology*
-
Two-Hybrid System Techniques
-
X-Linked Inhibitor of Apoptosis Protein
Substances
-
Apoptosis Regulatory Proteins
-
BEX3 protein, human
-
Carrier Proteins
-
DIABLO protein, human
-
Intracellular Signaling Peptides and Proteins
-
Membrane Glycoproteins
-
Mitochondrial Proteins
-
Proteins
-
TNF-Related Apoptosis-Inducing Ligand
-
TNFSF10 protein, human
-
Tumor Necrosis Factor-alpha
-
X-Linked Inhibitor of Apoptosis Protein
-
XIAP protein, human