FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis

Science. 1998 Mar 20;279(5358):1954-8. doi: 10.1126/science.279.5358.1954.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Apoptosis*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Doxorubicin / pharmacology
  • Embryonic and Fetal Development*
  • Endothelium, Vascular / embryology
  • Fas-Associated Death Domain Protein
  • Female
  • Gene Expression
  • Gene Targeting
  • Heart / embryology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Oncogenes
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / pharmacology
  • fas Receptor / genetics
  • fas Receptor / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Fadd protein, mouse
  • Fas-Associated Death Domain Protein
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Doxorubicin