Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction

Tanenobu Harada1, Atsushi Iwai, Tadaaki Miyazaki

  • 1Department of Bioresources, Hokkaido University Research Center for Zoonosis Control, North 20, West 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan.

Insights

Researchers discovered a new protein, death ligand signal enhancer (DELE), that binds to death associated protein 3 (DAP3) and enhances apoptosis signaling. DELE is crucial for apoptosis induction by death receptors like TNF-α and TRAIL.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Death associated protein 3 (DAP3) is a conserved protein regulating apoptosis.
  • The precise molecular mechanisms of DAP3-mediated apoptosis are not fully understood.

Purpose of the Study:

  • To identify novel proteins interacting with DAP3.
  • To elucidate the role of newly identified proteins in apoptosis signaling.

Main Methods:

  • Yeast two-hybrid screening to identify DAP3-binding proteins.
  • Mammalian cell culture and stable expression of identified proteins.
  • Apoptosis induction assays using TNF-α, TRAIL, and anti-Fas.
  • Western blotting to assess caspase activation.
  • siRNA-mediated knockdown of target gene expression.

Main Results:

  • A novel DAP3-binding protein, termed death ligand signal enhancer (DELE), was identified.
  • DELE binds to DAP3 in mammalian cells.
  • Overexpression of DELE sensitizes cells to TNF-α and TRAIL-induced apoptosis.
  • Knockdown of DELE expression confers resistance to apoptosis induced by TNF-α, TRAIL, and anti-Fas.
  • DELE knockdown inhibits the activation of caspase-3, caspase-8, and caspase-9.

Conclusions:

  • DELE plays a significant role in mediating apoptosis signals through death receptors.
  • DELE is a key regulator of the apoptotic pathway initiated by death ligands.

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