FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis
- PMID: 8617770
- DOI: 10.1074/jbc.271.9.4961
FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis
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- kappaB 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.
Similar articles
-
Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis.J Biol Chem. 2003 Jul 11;278(28):25534-41. doi: 10.1074/jbc.M303399200. Epub 2003 Apr 29. J Biol Chem. 2003. PMID: 12721308
-
Inhibition of death receptor-mediated gene induction by a cycloheximide-sensitive factor occurs at the level of or upstream of Fas-associated death domain protein (FADD).J Biol Chem. 2000 Aug 11;275(32):24357-66. doi: 10.1074/jbc.M000811200. J Biol Chem. 2000. PMID: 10823821
-
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.Cell. 1996 Jun 14;85(6):803-15. doi: 10.1016/s0092-8674(00)81265-9. Cell. 1996. PMID: 8681376
-
Exploring cell death mechanisms by analyzing signaling cascades of the TNF/NGF receptor family.Behring Inst Mitt. 1996 Oct;(97):144-55. Behring Inst Mitt. 1996. PMID: 8950472 Review.
-
Distinct adapter proteins mediate acid versus neutral sphingomyelinase activation through the p55 receptor for tumor necrosis factor.J Leukoc Biol. 1998 Jun;63(6):678-82. doi: 10.1002/jlb.63.6.678. J Leukoc Biol. 1998. PMID: 9620659 Review.
Cited by
-
Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms.J Cell Biol. 2002 Jun 10;157(6):975-84. doi: 10.1083/jcb.200204039. Epub 2002 Jun 3. J Cell Biol. 2002. PMID: 12045187 Free PMC article.
-
The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games.Immunology. 2005 May;115(1):1-20. doi: 10.1111/j.1365-2567.2005.02143.x. Immunology. 2005. PMID: 15819693 Free PMC article. Review.
-
Death effector domain protein PEA-15 potentiates Ras activation of extracellular signal receptor-activated kinase by an adhesion-independent mechanism.Mol Biol Cell. 2000 Sep;11(9):2863-72. doi: 10.1091/mbc.11.9.2863. Mol Biol Cell. 2000. PMID: 10982386 Free PMC article.
-
p38-mediated regulation of an Fas-associated death domain protein-independent pathway leading to caspase-8 activation during TGFbeta-induced apoptosis in human Burkitt lymphoma B cells BL41.Mol Biol Cell. 2001 Oct;12(10):3139-51. doi: 10.1091/mbc.12.10.3139. Mol Biol Cell. 2001. PMID: 11598198 Free PMC article.
-
Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases.Cell Death Dis. 2022 Mar 17;13(3):248. doi: 10.1038/s41419-022-04688-x. Cell Death Dis. 2022. PMID: 35301281 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
