FADD: Essential for Embryo Development and Signaling from Some, but Not All, Inducers of Apoptosis

• Published in: Science (American Association for the Advancement of Science) 1998-03, Vol.279 (5358), p.1954-1958
• Main Authors: Yeh, Wen-Chen, de la Pompa, José Luis, McCurrach, Mila E., Shu, Hong-Bing, Elia, Andrew J., Shahinian, Arda, Ng, Michelle, Wakeham, Andrew, Khoo, Wilson, Mitchell, Kyran, El-Deiry, Wafik S., Lowe, Scott W., Goeddel, David V.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adenoviruses; Animal embryology; Animals; Antibodies; Apoptosis; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell death; Cell lines; Cell Transformation, Neoplastic; Cells, Cultured; Cellular biology; Cellular signal transduction; Classical genetics, quantitative genetics, hybrids; Developmental Delays; Developmental Programs; Doxorubicin - pharmacology; Embryogenesis; Embryology; Embryonic and Fetal Development; Embryonic cells; Embryos; Endothelium, Vascular - embryology; fas Receptor - genetics; fas Receptor - physiology; Fas-Associated Death Domain Protein; Female; Fibroblasts; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Targeting; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Heart - embryology; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Myocardium; Oncogenes; Phenotypes; Pregnancy; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - physiology; Rodents; Signal Transduction; Tumor Necrosis Factor-alpha - pharmacology; Vertebrata
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.279.5358.1954

FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. 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. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.