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

K. Fu, H. Ren, Y. Wang, E. Fei, H. Wang, G. Wang

Research output: Contribution to journalArticle

Abstract

DJ-1 was initially identified as an oncogene product involved in human tumorigenesis in cooperation with Ras. Increased DJ-1 expression is associated with tumorigenesis in many cancers, whereas the loss of DJ-1 function is linked to an autosomal recessive form of Parkinson's disease (PD). It has been reported that DJ-1 protects cells from TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis. However, the mechanism by which DJ-1 is involved is still largely unknown. Here we show that DJ-1 inhibits TRAIL-induced apoptosis by blocking Fas-associated protein death domain (FADD)-mediated pro-caspase-8 activation. Wild-type DJ-1, but not the PD-associated mutant L166P, binds to FADD to inhibit the formation of the death-inducing signaling complex (DISC). DJ-1 competes with pro-caspase-8 to bind to FADD at the death effector domain, thereby repressing the recruitment and activation of pro-caspase-8 to the active form of caspase-8. Thus, our study suggests that DJ-1 protects against TRAIL-induced apoptosis through the regulation of DISC formation.

Original languageEnglish (US)
Pages (from-to)1311-1322
Number of pages12
JournalOncogene
Volume31
Issue number10
DOIs
StatePublished - Mar 8 2012

Keywords

  • DISC
  • DJ-1
  • FADD
  • TRAIL
  • apoptosis
  • caspase-8

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Fu, K., Ren, H., Wang, Y., Fei, E., Wang, H., & Wang, G. (2012). DJ-1 inhibits TRAIL-induced apoptosis by blocking pro-caspase-8 recruitment to FADD. Oncogene, 31(10), 1311-1322. https://doi.org/10.1038/onc.2011.315