Activation of Apoptosis Signal- Regulating Kinase 1 (ASK1) by the Adapter Protein Daxx
Howard Y. Chang,
*
Hideki Nishitoh,
*
Xiaolu Yang,
Hidenori Ichijo,
David Baltimore
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.
H. Y. Chang and X. Yang, Department of Biology, Massachusetts
Institute of Technology, Cambridge, MA 02138, USA. H. Nishitoh and H. Ichijo, Department of Biomaterials Science, Faculty of Dentistry, Tokyo
Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo
113-8549, and Department of Biochemistry, Cancer Institute, Tokyo,
Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro,
Toshima-ku, Tokyo 170, Japan. D. Baltimore, Department of Biology,
Massachusetts Institute of Technology, Cambridge, MA 02138, and
California Institute of Technology, Pasadena, CA 91125, USA.
*
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.
To whom correspondence should be addressed.
