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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Apoptosis / physiology*
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Arabidopsis Proteins*
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Blotting, Northern
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cloning, Molecular
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Co-Repressor Proteins
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DNA, Complementary
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Fatty Acid Desaturases / metabolism
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Gene Deletion
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins*
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JNK Mitogen-Activated Protein Kinases
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Mice
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Mitogen-Activated Protein Kinases*
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Molecular Chaperones
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Molecular Sequence Data
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Mutagenesis / physiology
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Nuclear Proteins*
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Plant Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA, Messenger / analysis
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Receptors, Cell Surface / metabolism
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Signal Transduction / physiology
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Yeasts / chemistry
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Yeasts / cytology
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Yeasts / enzymology
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fas Receptor / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Arabidopsis Proteins
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Carrier Proteins
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Co-Repressor Proteins
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DAXX protein, human
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DNA, Complementary
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Daxx protein, mouse
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Intracellular Signaling Peptides and Proteins
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Molecular Chaperones
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Nuclear Proteins
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Plant Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Receptors, Cell Surface
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fas Receptor
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Fatty Acid Desaturases
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Fad7 protein, Arabidopsis
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
Associated data
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GENBANK/AF006040
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GENBANK/AF050179