Volume 272, Number 46, Issue of November 14, 1997 pp. 28889-28894
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Requirement of Cysteine-rich Repeats of the Fas Receptor for Binding by the Fas Ligand

(Received for publication, August 6, 1997)

From the Department of Cell Biology and Anatomy, and ^§ Department of Medicine, Hospital for Special Surgery, Cornell University Medical College, New York, New York 10021

The Fas receptor is a member of a family of cell death receptors, including tumor necrosis factor receptor I (TNFR I), death receptor 3 and 4 (DR3 and DR4), and cytopathic avian receptor 1 (CAR1). The Fas receptor is composed of several discrete domains, including three cysteine-rich domains (CRDs), a transmembrane domain, and an intracellular domain responsible for transmitting an apoptotic signal. While the mechanism of Fas-mediated cell death has become elucidated, the requirements for Fas ligand binding to the receptor have not been fully defined. Using a series of chimeric F_c-receptor fusion proteins between the human Fas receptor and TNFR I, each cysteine-rich domain of Fas was found to be required for interaction with the Fas ligand. Interestingly, TNFR I CRD1 could partially substitute for the Fas CRD1. The importance of this domain was underscored by the analysis of a Fas extracellular mutation (C66R), which resulted in a complete loss of ligand binding. This mutation was cloned from a human patient suffering from Canale-Smith syndrome, which is characterized by autoimmunity resembling that observed in the lpr and lpr^cg mice. The localization of essential ligand binding domains in the Fas receptor correlated exactly with the ability of the Fas receptor fusion proteins to prevent cell death mediated by the Fas ligand.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Liu, J. N. Sarkaria, C. A. Petell, G. Paraskevakou, P. J. Zollman, M. Schroeder, B. Carlson, P. A. Decker, W. Wu, C. D. James, et al. Combination of Measles Virus Virotherapy and Radiation Therapy Has Synergistic Activity in the Treatment of Glioblastoma Multiforme Clin. Cancer Res., December 1, 2007; 13(23): 7155 - 7165. [Abstract] [Full Text] [PDF]

				P. Shrivastava, C. Pantano, R. Watkin, B. McElhinney, A. Guala, M. L. Poynter, R. L. Persinger, R. Budd, and Y. Janssen-Heininger Reactive Nitrogen Species-Induced Cell Death Requires Fas-Dependent Activation of c-Jun N-Terminal Kinase Mol. Cell. Biol., August 1, 2004; 24(15): 6763 - 6772. [Abstract] [Full Text] [PDF]

				R. M. Siegel, J. K. Frederiksen, D. A. Zacharias, F. K.-M. Chan, M. Johnson, D. Lynch, R. Y. Tsien, and M. J. Lenardo Fas Preassociation Required for Apoptosis Signaling and Dominant Inhibition by Pathogenic Mutations Science, June 30, 2000; 288(5475): 2354 - 2357. [Abstract] [Full Text]

				G. Papoff, P. Hausler, A. Eramo, M. G. Pagano, G. Di Leve, A. Signore, and G. Ruberti Identification and Characterization of a Ligand-independent Oligomerization Domain in the Extracellular Region of the CD95 Death Receptor J. Biol. Chem., December 31, 1999; 274(53): 38241 - 38250. [Abstract] [Full Text] [PDF]

				X.-M. Chen, G. J. Gores, C. V. Paya, and N. F. LaRusso Cryptosporidium parvum induces apoptosis in biliary epithelia by a Fas/Fas ligand-dependent mechanism Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G599 - G608. [Abstract] [Full Text] [PDF]

				K. Banki, E. Hutter, N. J. Gonchoroff, and A. Perl Molecular Ordering in HIV-induced Apoptosis. OXIDATIVE STRESS, ACTIVATION OF CASPASES, AND CELL SURVIVAL ARE REGULATED BY TRANSALDOLASE J. Biol. Chem., May 8, 1998; 273(19): 11944 - 11953. [Abstract] [Full Text] [PDF]