Science · 1998 · 595 citations · 22 references
Life SciencesCell BiologyMolecular BiologyApoptosisCell SignalingSignal TransductionApoptosis RegulationApoptotic Signal TransductionApoptotic SignalingCaspase ActivationDeath ReceptorsExtrinsic Apoptotic PathwayApoptosis Regulation By KinasesApoptosis Signaling PathwaysApoptosis-related Kinase CascadesCell Death Signaling PathwaysCell Surface Death ReceptorsJnk Pathway ActivationJnk Signaling PathwayNuclear Translocation Of Transcription Factors
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.
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