Daxx, a novel Fas-binding protein that activates JNK and apoptosis

Cell. 1997 Jun 27;89(7):1067-76. doi: 10.1016/s0092-8674(00)80294-9.

Abstract

The Fas cell surface receptor induces apoptosis upon receptor oligomerization. We have identified a novel signaling protein, termed Daxx, that binds specifically to the Fas death domain. Overexpression of Daxx enhances Fas-mediated apoptosis and activates the Jun N-terminal kinase (JNK) pathway. A C-terminal portion of Daxx interacts with the Fas death domain, while a different region activates both JNK and apoptosis. The Fas-binding domain of Daxx is a dominant-negative inhibitor of both Fas-induced apoptosis and JNK activation, while the FADD death domain partially inhibits death but not JNK activation. The Daxx apoptotic pathway is sensitive to both Bcl-2 and dominant-negative JNK pathway components and acts cooperatively with the FADD pathway. Thus, Daxx and FADD define two distinct apoptotic pathways downstream of Fas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology*
  • Arabidopsis Proteins*
  • Blotting, Northern
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cloning, Molecular
  • DNA, Complementary
  • Fatty Acid Desaturases / metabolism
  • Gene Deletion
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinases*
  • Molecular Chaperones
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Nuclear Proteins*
  • Plant Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / analysis
  • Receptors, Cell Surface / metabolism
  • Signal Transduction / physiology
  • Yeasts / chemistry
  • Yeasts / cytology
  • Yeasts / enzymology
  • fas Receptor / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Arabidopsis Proteins
  • Carrier Proteins
  • DAXX protein, human
  • DNA, Complementary
  • Daxx protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Nuclear Proteins
  • Plant Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptors, Cell Surface
  • fas Receptor
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases

Associated data

  • GENBANK/AF006040
  • GENBANK/AF050179