The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Fadd  -  Fas (TNFRSF6)-associated via death domain

Mus musculus

Synonyms: FAS-associated death domain protein, FAS-associating death domain-containing protein, Mediator of receptor induced toxicity, Mort1, Mort1/FADD, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Fadd

  • Here we demonstrate that expression of either CrmA, the cowpox virus serpin, or an inhibitor of the adapter protein FADD/MORT1 blocks Fas-mediated apoptosis but has no effect on BCR ligation-induced apoptosis of the B cell line WEHI-231 [1].
  • Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage [2].
  • Dominant negative MORT1/FADD rescues mice from CD95 and TNF-induced liver failure [3].
  • These data suggest a primary role for FADD/caspase-8 signaling that is necessary and sufficient for apoptosis of CMs subjected to hypoxia/SD [4].
  • METHODS: A FADD deletion mutant lacking the death effector domain was introduced into mice by transduction with an adenovirus vector, and the effect of this FADD dominant negative mutant was examined in several liver injury models [5].

High impact information on Fadd


Chemical compound and disease context of Fadd


Biological context of Fadd


Anatomical context of Fadd


Associations of Fadd with chemical compounds

  • In conclusion, our experiments provide evidence that MORT1/FADD is indispensable for Fas and TNF-mediated hepatic injury [3].
  • In one exception, replacing arginine 117 with an uncharged residue disrupted target binding and apoptosis signaling, but restoring the positive charge at position 117 failed to reconstitute the FADD function [11].
  • Western blot analysis also showed that alpha-tocotrienol did not induce FasL or FADD translocation from the cytosolic to membrane fraction in these cells [16].
  • In contrast, both GCDC and TCDC treatment resulted in Fas aggregation and recruitment of a dominant-negative FADD green fluorescent protein (GFP) and C360S procaspase 8-GFP to the plasma membrane [17].
  • In this study we report the interesting and unexpected result that actinomycin D increased the expression of FADD protein, and we demonstrate that other cellular stresses like ultraviolet irradiation or heat shock could also increase FADD levels in hepatocytes [18].

Physical interactions of Fadd


Regulatory relationships of Fadd


Other interactions of Fadd

  • We generated novel monoclonal antibodies specific for mouse FADD and caspase-8 to investigate whether cellular responses, apoptosis or proliferation, might be explained by differences in post-translational modification and subcellular localisation of these proteins [22].
  • In addition, interleukin-1-induced activation of A-SMase in FADD-deficient cells was unaltered [9].
  • In an in-depth study of the Fas/FasL-signaling pathway in thyroid tumor development, we have demonstrated that tumor cells specifically downregulate the multideath receptor adapter Fas-associated death domain (FADD) [12].
  • In particular, the TNF-R55-associated protein FADD seems to be responsible for recruitment and subsequent activation of caspase 8 [9].
  • Fas-associated death domain (FADD) and caspase-8 are key signal transducers for death receptor-induced apoptosis, whereas cellular FLICE-inhibitory protein (cFLIP) antagonizes this process [23].

Analytical, diagnostic and therapeutic context of Fadd

  • In primary embryonic fibroblasts from FADD-deficient mice the activation of A-SMase by TNF-R55 ligation was almost completely impaired [9].
  • Immunoprecipitates of fas antigen from membrane preparations made from control or castrated rat prostates were analyzed for coprecipitation of FADD and RIP proteins to assess the activation state of the fas antigen before and after castration [24].
  • Purified peripheral FADD-deficient T cells failed to undergo extensive homeostatic expansion after adoptive transfer into lymphocyte-deficient hosts, and responded poorly to proliferation induced by ex vivo TCR stimulation [25].
  • PyLT-Ag co-precipitated following immunoprecipitation of caspase-8 or FADD, both components of the DISC [26].
  • The expression of protein and mRNA of FADD were detected by immunohistochemistry and PT-PCR [21].


  1. Rapid B cell apoptosis induced by antigen receptor ligation does not require Fas (CD95/APO-1), the adaptor protein FADD/MORT1 or CrmA-sensitive caspases but is defective in both MRL-+/+ and MRL-lpr/lpr mice. Yoshida, T., Higuchi, T., Hagiyama, H., Strasser, A., Nishioka, K., Tsubata, T. Int. Immunol. (2000) [Pubmed]
  2. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Yeh, W.C., Pompa, J.L., McCurrach, M.E., Shu, H.B., Elia, A.J., Shahinian, A., Ng, M., Wakeham, A., Khoo, W., Mitchell, K., El-Deiry, W.S., Lowe, S.W., Goeddel, D.V., Mak, T.W. Science (1998) [Pubmed]
  3. Dominant negative MORT1/FADD rescues mice from CD95 and TNF-induced liver failure. Schuchmann, M., Varfolomeev, E.E., Hermann, F., Rueckert, F., Strand, D., Koehler, H., Strand, S., Lohse, A.W., Wallach, D., Galle, P.R. Hepatology (2003) [Pubmed]
  4. Importance of FADD signaling in serum deprivation- and hypoxia-induced cardiomyocyte apoptosis. Chao, W., Shen, Y., Li, L., Rosenzweig, A. J. Biol. Chem. (2002) [Pubmed]
  5. Protection against Fas-mediated and tumor necrosis factor receptor 1-mediated liver injury by blockade of FADD without loss of nuclear factor-kappaB activation. Seino, K., Setoguchi, Y., Ogino, T., Kayagaki, N., Akiba, H., Nakano, H., Taniguchi, H., Takada, Y., Yuzawa, K., Todoroki, T., Fukuchi, Y., Yagita, H., Okumura, K., Fukao, K. Ann. Surg. (2001) [Pubmed]
  6. A function of Fas-associated death domain protein in cell cycle progression localized to a single amino acid at its C-terminal region. Hua, Z.C., Sohn, S.J., Kang, C., Cado, D., Winoto, A. Immunity (2003) [Pubmed]
  7. FADD null mouse embryonic fibroblasts undergo apoptosis after photosensitization with the silicon phthalocyanine Pc 4. Nagy, B., Yeh, W.C., Mak, T.W., Chiu, S.M., Separovic, D. Arch. Biochem. Biophys. (2001) [Pubmed]
  8. A mouse Fas-associated protein with homology to the human Mort1/FADD protein is essential for Fas-induced apoptosis. Zhang, J., Winoto, A. Mol. Cell. Biol. (1996) [Pubmed]
  9. Requirement of FADD for tumor necrosis factor-induced activation of acid sphingomyelinase. Wiegmann, K., Schwandner, R., Krut, O., Yeh, W.C., Mak, T.W., Krönke, M. J. Biol. Chem. (1999) [Pubmed]
  10. Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Yeh, W.C., Itie, A., Elia, A.J., Ng, M., Shu, H.B., Wakeham, A., Mirtsos, C., Suzuki, N., Bonnard, M., Goeddel, D.V., Mak, T.W. Immunity (2000) [Pubmed]
  11. Structural requirements for signal-induced target binding of FADD determined by functional reconstitution of FADD deficiency. Imtiyaz, H.Z., Zhang, Y., Zhang, J. J. Biol. Chem. (2005) [Pubmed]
  12. Loss of FADD protein expression results in a biased Fas-signaling pathway and correlates with the development of tumoral status in thyroid follicular cells. Tourneur, L., Mistou, S., Michiels, F.M., Devauchelle, V., Renia, L., Feunteun, J., Chiocchia, G. Oncogene (2003) [Pubmed]
  13. Ionizing radiation and chemotherapeutic drugs induce apoptosis in lymphocytes in the absence of Fas or FADD/MORT1 signaling. Implications for cancer therapy. Newton, K., Strasser, A. J. Exp. Med. (2000) [Pubmed]
  14. Sensitivity of photoreceptor-derived cell line (661W) to baculoviral p35, Z-VAD.FMK, and Fas-associated death domain. Tuohy, G., Millington-Ward, S., Kenna, P.F., Humphries, P., Farrar, G.J. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  15. Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95-driven apoptosis. Falsig, J., Latta, M., Leist, M. J. Neurochem. (2004) [Pubmed]
  16. Intracellular mechanisms mediating tocotrienol-induced apoptosis in neoplastic mammary epithelial cells. Sylvester, P.W., Shah, S. Asia Pacific journal of clinical nutrition. (2005) [Pubmed]
  17. The bile acid-activated phosphatidylinositol 3-kinase pathway inhibits Fas apoptosis upstream of bid in rodent hepatocytes. Takikawa, Y., Miyoshi, H., Rust, C., Roberts, P., Siegel, R., Mandal, P.K., Millikan, R.E., Gores, G.J. Gastroenterology (2001) [Pubmed]
  18. Hepatocyte Fas-associating death domain protein/mediator of receptor-induced toxicity (FADD/MORT1) levels increase in response to pro-apoptotic stimuli. Kim, P.K., Wang, Y., Gambotto, A., Kim, Y.M., Weller, R., Zuckerbraun, B.S., Hua, Y., Watkins, S.C., Billiar, T.R. J. Biol. Chem. (2002) [Pubmed]
  19. Effects of a dominant interfering mutant of FADD on signal transduction in activated T cells. Newton, K., Kurts, C., Harris, A.W., Strasser, A. Curr. Biol. (2001) [Pubmed]
  20. p53-dependent impairment of T-cell proliferation in FADD dominant-negative transgenic mice. Zörnig, M., Hueber, A.O., Evan, G. Curr. Biol. (1998) [Pubmed]
  21. mRNA and protein expression of Fas associated death domain protein in apoptosic hepatocyte induced by tumor necrosis factor-alpha. Zhang, G., Zhou, X., Wang, C., Yao, M., Yu, H., Xie, Q. Zhonghua Gan Zang Bing Za Zhi (2001) [Pubmed]
  22. Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes. O'Reilly, L.A., Divisekera, U., Newton, K., Scalzo, K., Kataoka, T., Puthalakath, H., Ito, M., Huang, D.C., Strasser, A. Cell Death Differ. (2004) [Pubmed]
  23. Cellular FLICE-inhibitory protein is required for T cell survival and cycling. Chau, H., Wong, V., Chen, N.J., Huang, H.L., Lin, W.J., Mirtsos, C., Elford, A.R., Bonnard, M., Wakeham, A., You-Ten, A.I., Lemmers, B., Salmena, L., Pellegrini, M., Hakem, R., Mak, T.W., Ohashi, P., Yeh, W.C. J. Exp. Med. (2005) [Pubmed]
  24. Fas antigen/CD-95 upregulation and activation during castration-induced regression of the rat ventral prostate gland. de la Taille, A., Chen, M.W., Shabsigh, A., Bagiella, E., Kiss, A., Buttyan, R. Prostate (1999) [Pubmed]
  25. Conditional Fas-associated death domain protein (FADD): GFP knockout mice reveal FADD is dispensable in thymic development but essential in peripheral T cell homeostasis. Zhang, Y., Rosenberg, S., Wang, H., Imtiyaz, H.Z., Hou, Y.J., Zhang, J. J. Immunol. (2005) [Pubmed]
  26. Polyomavirus large T-antigen protects mouse cells from Fas-, TNF-alpha- and taxol-induced apoptosis. Rodier, F., Bertrand, R., Bossolasco, M., Mes-Masson, A.M. Oncogene (2000) [Pubmed]
WikiGenes - Universities