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Activation of Apoptosis Signal-Regulating Kinase 1 (ASK1) by the Adapter Protein Daxx

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Science  18 Sep 1998:
Vol. 281, Issue 5384, pp. 1860-1863
DOI: 10.1126/science.281.5384.1860

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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.

  • * These authors contributed equally to this work.

  • Present address: Department of Molecular and Cellular Engineering and Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104, USA.

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