MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kataoka, T.
Right arrow Articles by Tschopp, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kataoka, T.
Right arrow Articles by Tschopp, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2004, p. 2627-2636, Vol. 24, No. 7
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.7.2627-2636.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

N-Terminal Fragment of c-FLIP(L) Processed by Caspase 8 Specifically Interacts with TRAF2 and Induces Activation of the NF-{kappa}B Signaling Pathway

Takao Kataoka1* and Jürg Tschopp2

Division of Bioinformatics, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8501, Japan,1 Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland2

Received 22 October 2003/ Returned for modification 21 November 2003/ Accepted 5 January 2004

Caspase 8 is required not only for death receptor-mediated apoptosis but also for lymphocyte activation in the immune system. FLIP(L), the long-splice form of c-FLIP, is one of the specific substrates for caspase 8, and increased expression of FLIP(L) promotes activation of the NF-{kappa}B signaling pathway. The synthetic caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) markedly blocked NF-{kappa}B activation induced by overexpression of FLIP(L). FLIP(L) is specifically processed by caspase 8 into N-terminal FLIP(p43) and C-terminal FLIP(p12). Only FLIP(p43) was able to induce NF-{kappa}B activation as efficiently as FLIP(L), and FLIP(p43)-induced NF-{kappa}B activation became insensitive to zVAD-fmk. In caspase 8-deficient cells, FLIP(p43) provoked NF-{kappa}B activation only when procaspase 8 or caspase 8(p43) was complemented. FLIP(p43)-induced NF-{kappa}B activation was profoundly blocked by the dominant-negative TRAF2. Moreover, endogenous TRAF2 interacted specifically with FLIP(p43), and the formation of the FLIP(p43)-caspase 8-TRAF2 tertiary complex was a prerequisite to induction of NF-{kappa}B activation. zVAD-fmk prevented the recruitment of TRAF2 into the death-inducing signaling complex. Thus, our present results demonstrate that FLIP(p43) processed by caspase 8 specifically interacts with TRAF2 and subsequently induces activation of the NF-{kappa}B signaling pathway.

* Corresponding author. Mailing address: Division of Bioinformatics, Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. Phone: 81-45-924-5830. Fax: 81-45-924-5832. E-mail: tkataoka{at}bio.titech.ac.jp.

Molecular and Cellular Biology, April 2004, p. 2627-2636, Vol. 24, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.7.2627-2636.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2004 by the American Society for Microbiology. All rights reserved.