Abstract
The Fas death receptor can activate the Jun NH2-terminal kinase (JNK) pathway through the receptor-associated protein Daxx. Daxx was found to activate the JNK kinase kinase ASK1, and overexpression of a kinase-deficient ASK1 mutant inhibited Fas- and Daxx-induced apoptosis and JNK activation. Fas activation induced Daxx to interact with ASK1, which consequently relieved an inhibitory intramolecular interaction between the amino- and carboxyl-termini of ASK1, activating its kinase activity. The Daxx-ASK1 connection completes a signaling pathway from a cell surface death receptor to kinase cascades that modulate nuclear transcription factors.
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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Alleles
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Amino Acid Sequence
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Animals
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Apoptosis*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carrier Proteins / metabolism*
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Cell Line
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Co-Repressor Proteins
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Enzyme Activation
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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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MAP Kinase Kinase Kinases
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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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Nuclear Proteins*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Tumor Cells, Cultured
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fas Receptor / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Co-Repressor Proteins
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DAXX protein, human
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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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Recombinant Fusion Proteins
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fas Receptor
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Protein Serine-Threonine Kinases
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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
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MAP Kinase Kinase Kinases