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Daxx, a Novel Fas-Binding Protein That Activates JNK and Apoptosis

Yang, Xiaolu and Khosravi-Far, Roya and Chang, Howard Y. and Baltimore, David (1997) Daxx, a Novel Fas-Binding Protein That Activates JNK and Apoptosis. Cell, 89 (7). pp. 1067-1076. ISSN 0092-8674. PMCID PMC2989411. doi:10.1016/s0092-8674(00)80294-9.

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The Fas cell surface receptor induces apoptosis upon receptor oligomerization. We have identified a novel signaling protein, termed Daxx, that binds specifically to the Fas death domain. Overexpression of Daxx enhances Fas-mediated apoptosis and activates the Jun N-terminal kinase (JNK) pathway. A C-terminal portion of Daxx interacts with the Fas death domain, while a different region activates both JNK and apoptosis. The Fas-binding domain of Daxx is a dominant-negative inhibitor of both Fas-induced apoptosis and JNK activation, while the FADD death domain partially inhibits death but not JNK activation. The Daxx apoptotic pathway is sensitive to both Bcl-2 and dominant-negative JNK pathway components and acts cooperatively with the FADD pathway. Thus, Daxx and FADD define two distinct apoptotic pathways downstream of Fas.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© 1997 Cell Press. Under an Elsevier user license. Received 8 January 1997, Revised 8 May 1997. Correspondence regarding this paper should be addressed to D. B. We are indebted to Dr. Genhong Cheng for his help in the initial phase of this project. We thank Drs. R. Brent, Y. W. Choi, C. J. Der, D. V. Goeddel, A. Hoffmann, M. Karin, R. N. Kolesnick, P. H. Krammer, R. J. Lutz, S. Nagata, R. Treisman, D. Wallach, and J. Yuan their generous gifts of reagents, and S. W. Fesik for examining the Daxx sequence. We thank P. Svec and Y. Li for excellent technical assistance, and Drs. A. J. Koleske, B. Chen, Z. Songyang, Y. Yamanashi, I. Stancovsky and other members of Baltimore lab for valuable advice. X. Y. and R. K.-F. are fellows of the Leukemia Society of America and Irvington Research Institute, respectively. H. Y. C. is supported by the Medical Scientist Training Program at Harvard Medical School. D. B. is an American Cancer Society Research Professor. This work was supported by the NIH grant CA51462.
Funding AgencyGrant Number
Leukemia Society of AmericaUNSPECIFIED
Irvington Institute for Medical ResearchUNSPECIFIED
Harvard Medical SchoolUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Issue or Number:7
PubMed Central ID:PMC2989411
Record Number:CaltechAUTHORS:20200422-150958917
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Official Citation:Xiaolu Yang, Roya Khosravi-Far, Howard Y Chang, David Baltimore, Daxx, a Novel Fas-Binding Protein That Activates JNK and Apoptosis, Cell, Volume 89, Issue 7, 1997, Pages 1067-1076, ISSN 0092-8674,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102729
Deposited By: George Porter
Deposited On:23 Apr 2020 16:07
Last Modified:16 Nov 2021 18:14

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