HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 31, 32780-32785, July 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/31/32780    most recent M401680200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomas, L. R. Articles by Thorburn, A. Search for Related Content PubMed PubMed Citation Articles by Thomas, L. R. Articles by Thorburn, A. Social Bookmarking                      What's this?

Direct Binding of Fas-associated Death Domain (FADD) to the Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor DR5 Is Regulated by the Death Effector Domain of FADD^*

Lance R. Thomas, Adrianna Henson, John C. Reed, Freddie R. Salsbury¶, and Andrew Thorburn||

From the Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Medical Center Blvd. Winston-Salem, North Carolina 27157, the Burnham Institute, La Jolla, California 92037, and the ^¶Department of Physics, Wake Forest University, Winston-Salem, North Carolina 27109

Members of the tumor necrosis factor superfamily of receptors induce apoptosis by recruiting adaptor molecules through death domain interactions. The central adaptor molecule for these receptors is the death domain-containing protein Fas-associated death domain (FADD). FADD binds a death domain on a receptor or additional adaptor and recruits caspases to the activated receptor. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signals apoptosis through two receptors, DR4 and DR5. Although there is much interest in TRAIL, the mechanism by which FADD is recruited to the TRAIL receptors is not clear. Using a reverse two-hybrid system we previously identified mutations in the death effector domain of FADD that prevented binding to Fas/CD95. Here we show that these mutations also prevent binding to DR5. FADD-deficient Jurkat cells stably expressing these FADD mutations did not transduce TRAIL or Fas/CD95 signaling. Second site compensating mutations that restore binding to and signaling through Fas/CD95 and DR5 were also in the death effector domain. We conclude that in contrast to current models where the death domain of FADD functions independently of the death effector domain, the death effector domain of FADD comes into direct contact with both TRAIL and Fas/CD95 receptors.

Received for publication, February 16, 2004 , and in revised form, June 1, 2004.

^* This work was supported by grants from the Susan G. Komen Breast Cancer Foundation (to L. R. T.), the United States Army Breast Cancer Research Program (to L. R. T. and A. T.), and National Institutes of Health Grant GM61694 (to J. C. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed. Tel.: 336-716-7587; Fax: 336-716-0255; E-mail: athorbur{at}wfubmc.edu.

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

This article has been cited by other articles:

				L. Bin, J. Thorburn, L. R. Thomas, P. E. Clark, R. Humphreys, and A. Thorburn Tumor-derived Mutations in the TRAIL Receptor DR5 Inhibit TRAIL Signaling through the DR4 Receptor by Competing for Ligand Binding J. Biol. Chem., September 21, 2007; 282(38): 28189 - 28194. [Abstract] [Full Text] [PDF]

				K. Behbakht, L. Qamar, C. S. Aldridge, R. D. Coletta, S. A. Davidson, A. Thorburn, and H. L. Ford Six1 Overexpression in Ovarian Carcinoma Causes Resistance to TRAIL-Mediated Apoptosis and Is Associated with Poor Survival Cancer Res., April 1, 2007; 67(7): 3036 - 3042. [Abstract] [Full Text] [PDF]

				J. J. Song, J. Y. An, Y. T. Kwon, and Y. J. Lee Evidence for Two Modes of Development of Acquired Tumor Necrosis Factor-related Apoptosis-inducing Ligand Resistance: INVOLVEMENT OF Bcl-xL J. Biol. Chem., January 5, 2007; 282(1): 319 - 328. [Abstract] [Full Text] [PDF]

				Y. Akasaki, G. Liu, H. H. Matundan, H. Ng, X. Yuan, Z. Zeng, K. L. Black, and J. S. Yu A Peroxisome Proliferator-activated Receptor-{gamma} Agonist, Troglitazone, Facilitates Caspase-8 and -9 Activities by Increasing the Enzymatic Activity of Protein-tyrosine Phosphatase-1B on Human Glioma Cells J. Biol. Chem., March 10, 2006; 281(10): 6165 - 6174. [Abstract] [Full Text] [PDF]

				C. Sandu, E. Gavathiotis, T. Huang, I. Wegorzewska, and M. H. Werner A Mechanism for Death Receptor Discrimination by Death Adaptors J. Biol. Chem., September 9, 2005; 280(36): 31974 - 31980. [Abstract] [Full Text] [PDF]

				J. Thorburn, F. Moore, A. Rao, W. W. Barclay, L. R. Thomas, K. W. Grant, S. D. Cramer, and A. Thorburn Selective Inactivation of a Fas-associated Death Domain Protein (FADD)-dependent Apoptosis and Autophagy Pathway in Immortal Epithelial Cells Mol. Biol. Cell, March 1, 2005; 16(3): 1189 - 1199. [Abstract] [Full Text] [PDF]

				L. R. Thomas, R. L. Johnson, J. C. Reed, and A. Thorburn The C-terminal Tails of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) and Fas Receptors Have Opposing Functions in Fas-associated Death Domain (FADD) Recruitment and Can Regulate Agonist-specific Mechanisms of Receptor Activation J. Biol. Chem., December 10, 2004; 279(50): 52479 - 52486. [Abstract] [Full Text] [PDF]