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Science 288 (5475): 2354-2357

Copyright © 2000 by the American Association for the Advancement of Science

Fas Preassociation Required for Apoptosis Signaling and Dominant Inhibition by Pathogenic Mutations

Richard M. Siegel, 1 John K. Frederiksen, 1 David A. Zacharias, 2 Francis Ka-Ming Chan, 1 Michele Johnson, 1 David Lynch, 3 Roger Y. Tsien, 2 Michael J. Lenardo 1*

Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.

1 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2 Howard Hughes Medical Institute and Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
3 Immunex Corporation, 51 University Street, Seattle, WA 98101, USA.
*   To whom correspondence should be addressed. E-mail: lenardo{at}nih.gov



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LF 15-0195 immunosuppressive agent enhances activation-induced T-cell death by facilitating caspase-8 and caspase-10 activation at the DISC level.
P. Ducoroy, O. Micheau, S. Perruche, L. Dubrez-Daloz, D. de Fornel, P. Dutartre, P. Saas, and E. Solary (2003)
Blood 101, 194-201
   Abstract »    Full Text »    PDF »
Fas Activation Induces Renal Tubular Epithelial Cell beta 8 Integrin Expression and Function in the Absence of Apoptosis.
G. Jarad, B. Wang, S. Khan, J. DeVore, H. Miao, K. Wu, S. L. Nishimura, B. A. Wible, M. Konieczkowski, J. R. Sedor, et al. (2002)
J. Biol. Chem. 277, 47826-47833
   Abstract »    Full Text »    PDF »
The Long Form of FLIP Is an Activator of Caspase-8 at the Fas Death-inducing Signaling Complex.
O. Micheau, M. Thome, P. Schneider, N. Holler, J. Tschopp, D. W. Nicholson, C. Briand, and M. G. Grutter (2002)
J. Biol. Chem. 277, 45162-45171
   Abstract »    Full Text »    PDF »
A Novel Splice Variant of the Fas Gene in Patients with Cutaneous T-Cell Lymphoma.
R. van Doorn, R. Dijkman, M. H. Vermeer, T. M. Starink, R. Willemze, and C. P. Tensen (2002)
Cancer Res. 62, 5389-5392
   Abstract »    Full Text »    PDF »
Seeing the Light: Preassembly and Ligand-Induced Changes of the Interferon {gamma} Receptor Complex in Cells.
C. D. Krause, E. Mei, J. Xie, Y. Jia, M. A. Bopp, R. M. Hochstrasser, and S. Pestka (2002)
Mol. Cell. Proteomics 1, 805-815
   Abstract »    Full Text »    PDF »
Disabling Receptor Ensembles with Rationally Designed Interface Peptidomimetics.
A. Berezov, J. Chen, Q. Liu, H.-T. Zhang, M. I. Greene, and R. Murali (2002)
J. Biol. Chem. 277, 28330-28339
   Abstract »    Full Text »    PDF »
Resistance to Infection by Subgroups B, D, and E Avian Sarcoma and Leukosis Viruses Is Explained by a Premature Stop Codon within a Resistance Allele of the tvb Receptor Gene.
S. Klucking, H. B. Adkins, and J. A. T. Young (2002)
J. Virol. 76, 7918-7921
   Abstract »    Full Text »    PDF »
Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue.
J. F. Panus, C. A. Smith, C. A. Ray, T. D. Smith, D. D. Patel, and D. J. Pickup (2002)
PNAS 99, 8348-8353
   Abstract »    Full Text »    PDF »
A Fifteen-Amino-Acid TVB Peptide Serves as a Minimal Soluble Receptor for Subgroup B Avian Leukosis and Sarcoma Viruses.
D. J. Knauss and J. A. T. Young (2002)
J. Virol. 76, 5404-5410
   Abstract »    Full Text »    PDF »
Fas-Dependent Elimination of Nonselected CD8 Cells and lpr Disease.
L. A. Trimble, K. A. Prince, G. A. Pestano, J. Daley, and H. Cantor (2002)
J. Immunol. 168, 4960-4967
   Abstract »    Full Text »    PDF »
Sticky Caveats in an Otherwise Glowing Report: Oligomerizing Fluorescent Proteins and Their Use in Cell Biology.
D. A. Zacharias (2002)
Sci. STKE 2002, pe23
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor Receptor 1 Is an ATPase Regulated by Silencer of Death Domain.
K. Miki and E. M. Eddy (2002)
Mol. Cell. Biol. 22, 2536-2543
   Abstract »    Full Text »    PDF »
Amyloid beta Binds Trimers as Well as Monomers of the 75-kDa Neurotrophin Receptor and Activates Receptor Signaling.
M. Yaar, S. Zhai, R. E. Fine, P. B. Eisenhauer, B. L. Arble, K. B. Stewart, and B. A. Gilchrest (2002)
J. Biol. Chem. 277, 7720-7725
   Abstract »    Full Text »    PDF »
All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction.
J. Y. Chung, Y. C. Park, H. Ye, and H. Wu (2002)
J. Cell Sci. 115, 679-688
   Abstract »    Full Text »    PDF »
An essential role for membrane rafts in the initiation of Fas/CD95-triggered cell death in mouse thymocytes.
A.-O. Hueber, A.-M. Bernard, Z. Herincs, A. Couzinet, and H.-T. He (2002)
EMBO Rep. 3, 190-196
   Abstract »    Full Text »    PDF »
Phorbol 12-myristate 13-Acetate Inhibits Death Receptor-mediated Apoptosis in Jurkat Cells by Disrupting Recruitment of Fas-associated Polypeptide with Death Domain.
X. W. Meng, M. P. Heldebrant, and S. H. Kaufmann (2002)
J. Biol. Chem. 277, 3776-3783
   Abstract »    Full Text »    PDF »
Binding of FADD and Caspase-8 to Molluscum Contagiosum Virus MC159 v-FLIP Is Not Sufficient for Its Antiapoptotic Function.
T. L. Garvey, J. Bertin, R. M. Siegel, G.-h. Wang, M. J. Lenardo, and J. I. Cohen (2002)
J. Virol. 76, 697-706
   Abstract »    Full Text »    PDF »

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