Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx

HY Chang, H Nishitoh, X Yang, H Ichijo, D Baltimore - Science, 1998 - science.org
HY Chang, H Nishitoh, X Yang, H Ichijo, D Baltimore
Science, 1998science.org
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 …
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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