Direct interaction of Smac with NADE promotes TRAIL-induced apoptosis

Biochem Biophys Res Commun. 2004 Jun 25;319(2):649-54. doi: 10.1016/j.bbrc.2004.05.043.


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


  • 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