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Dissecting Fas signaling with an altered-specificity death-domain mutant: Requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation

Chang, Howard Y. and Yang, Xiaolu and Baltimore, David (1999) Dissecting Fas signaling with an altered-specificity death-domain mutant: Requirement of FADD binding for apoptosis but not Jun N-terminal kinase activation. Proceedings of the National Academy of Sciences of the United States of America, 96 (4). pp. 1252-1256. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:CHApnas99

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Abstract

Fas is a cell surface death receptor that regulates peripheral tolerance and lymphoid homeostasis. In many pathologic conditions, ectopic Fas activation mediates tissue destruction. Several proteins that can bind to the cytoplasmic death domain of Fas have been implicated in Fas signal transduction. Here we show that FADD, which couples Fas to pro-caspase-8, and, Daxx, which couples Fas to the Jun N-terminal kinase pathway, bind independently to the Fas death domain. We have isolated a death domain mutant, termed Fas delta, that selectively binds Daxx but not FADD. In tranfected tissue culture cells, Fas delta activated Jun N-terminal kinase normally but was impaired in cell death induction. These results suggest that FADD and Daxx activate two independent pathways downstream of Fas and confirm the essential role of FADD binding in apoptosis induction.


Item Type:Article
Additional Information:© 1999 by The National Academy of Sciences. Contributed by David Baltimore, December 18, 1998. We thank B. Huang, S. Fesik, and D. V. Goeddel for generous gifts of reagents, and members of the Baltimore lab for discussions and encouragement. This work was supported by the Medical Scientist Training Program at Harvard Medical School (H.Y.C.), Leukemia Society of America (X.Y.), and National Institutes of Health Grant CA51462.
Subject Keywords:KAPPA-B ACTIVATION, TNF RECEPTOR, CELL-DEATH, LYMPHOPROLIFERATIVE SYNDROME, PROTEIN, ANTIGEN, MUTATIONS, GENE, INVOLVEMENT, EXPRESSION
Record Number:CaltechAUTHORS:CHApnas99
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:CHApnas99
Alternative URL:http://www.pnas.org/cgi/content/abstract/96/4/1252
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:571
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Aug 2005
Last Modified:14 Nov 2014 19:18

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