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DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD

K Fu1, H Ren, Y Wang

  • 1Laboratory of Molecular Neuropathology, Department of Neurobiology, Key Laboratory of Brain Function and Disease and School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, Anhui, PR China.

Oncogene
|July 26, 2011
PubMed

Insights

DJ-1 protein guards cells against programmed cell death (apoptosis) induced by TRAIL. It achieves this by preventing the assembly of the death-inducing signaling complex (DISC), a key step in apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • DJ-1 is implicated in human tumorigenesis and Parkinson's disease (PD).
  • DJ-1 is known to protect cells from TRAIL-induced apoptosis, but the underlying mechanism remains unclear.
  • TRAIL-induced apoptosis is a critical cellular process regulated by death-inducing signaling complexes (DISCs).

Purpose of the Study:

  • To elucidate the mechanism by which DJ-1 inhibits TRAIL-induced apoptosis.
  • To investigate the interaction between DJ-1 and components of the apoptosis signaling pathway.

Main Methods:

  • Investigated the role of DJ-1 in TRAIL-induced apoptosis.
  • Utilized wild-type and PD-associated mutant L166P DJ-1.
  • Examined the binding of DJ-1 to Fas-associated protein death domain (FADD).
  • Assessed the formation of the death-inducing signaling complex (DISC) and pro-caspase-8 activation.

Main Results:

  • Wild-type DJ-1, but not the L166P mutant, binds to FADD.
  • DJ-1 binding to FADD inhibits the formation of the DISC.
  • DJ-1 competes with pro-caspase-8 for FADD binding, thereby preventing pro-caspase-8 activation.

Conclusions:

  • DJ-1 protects against TRAIL-induced apoptosis by directly inhibiting DISC formation.
  • DJ-1's interaction with FADD is crucial for its anti-apoptotic function.
  • Dysregulation of DJ-1's interaction with FADD may contribute to diseases like PD and cancer.

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