FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis

Arul M. Chinnaiyan, Clifford G Tepper, Michael F Seldin, Karen O'Rourke, Frank C. Kischkel, Stefan Hellbardt, Peter H. Krammer, Marcus E. Peter, Vishva M. Dixit

Research output: Contribution to journalArticle

688 Scopus citations

Abstract

CD95 (Fas/APO-1) and tumor necrosis factor receptor-1 (TNFR-1) are related molecules that signal apoptosis. Recently, a number of novel binding proteins have been proposed to mediate the signaling of these death receptors. Here we report that an N-terminal truncation of one of these candidate signal transducers, FADD/MORT1, abrogates CD95-induced apoptosis, ceramide generation, and activation of the cell death protease Yama/CPP32. In addition, this dominant-negative derivative of FADD (FADD-DN) blocked TNF- induced apoptosis while not affecting NF-κB activation. FADD-DN bound both receptors, and in the case of CD95, it disrupted the assembly of a signaling complex. Taken together, our results functionally establish FADD as the apoptotic trigger of CD95 and TNFR-1.

Original languageEnglish (US)
Pages (from-to)4961-4965
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number9
DOIs
StatePublished - Mar 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Chinnaiyan, A. M., Tepper, C. G., Seldin, M. F., O'Rourke, K., Kischkel, F. C., Hellbardt, S., Krammer, P. H., Peter, M. E., & Dixit, V. M. (1996). FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. Journal of Biological Chemistry, 271(9), 4961-4965. https://doi.org/10.1074/jbc.271.9.4961