The Death Effector Domain-associated Factor Plays Distinct Regulatory Roles in the Nucleus and Cytoplasm

Lixin Zheng, Olaf Schickling, Marcus E. Peter, Michael J. Lenardo*

*Corresponding author for this work

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Homophilic interactions of death effector domains (DEDs) are crucial for the signaling pathways of death receptor-mediated apoptosis. The machinery that regulates proper oligomerization and autoactivation of procaspase-8 and/or procaspase-10 during T lymphocyte activation determines whether the cells will undergo caspase-mediated apoptosis or proliferation. We screened a yeast two-hybrid library by using the DEDs contained in the prodomains of procaspase-8 and procaspase-10 and isolated a DED-associated factor (DEDAF) that interacts with several DED-containing proteins but does not itself contain a DED. DEDAF is highly conserved between human and mouse (98% amino acid identity) and is homologous to a nuclear regulatory protein YAF-2. DEDAF is expressed at the highest levels in lymphoid tissues and placenta. DEDAF interacts with FADD, procaspase-8, and procaspase-10 in the cytosol as well as with the DED-containing DNA-binding protein (DEDD) in the nucleus. At the cell membrane, DEDAF augmented the formation of CD95-FADD-caspase-8 complexes and enhanced death receptoras well as DED-mediated apoptosis. In the nucleus, DEDAF caused the DEDD protein to relocalize from subnuclear structures to a diffuse distribution in the nucleoplasm. Our data therefore suggest that DEDAF may be involved in the regulation of both cytoplasmic and nuclear events of apoptosis.

Original languageEnglish (US)
Pages (from-to)31945-31952
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number34
DOIs
StatePublished - Aug 24 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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