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J. Biol. Chem., Vol. 280, Issue 33, 29637-29644, August 19, 2005

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CD47 Augments Fas/CD95-mediated Apoptosis^*

Partha P. Manna, Julie Dimitry, Per-Arne Oldenborg, and William A. Frazier¶

From the Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110 and the Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umea University, SE-901 87 Umea, Sweden

Fas (CD95) mediates apoptosis of many cell types, but the susceptibility of cells to killing by Fas ligand and anti-Fas antibodies is highly variable. Jurkat T cells lacking CD47 (integrin-associated protein) are relatively resistant to Fas-mediated death but are efficiently killed by Fas ligand or anti-Fas IgM (CH11) upon expression of CD47. Lack of CD47 impairs events downstream of Fas activation including caspase activation, poly-(ADP-ribose) polymerase cleavage, cytochrome c release from mitochondria, loss of mitochondrial membrane potential, and DNA cleavage. Neither CD47 signaling nor raft association of CD47 is required to enable Fas apoptosis. CH11 induces association of Fas and CD47. Primary T cells from CD47-null mice are also protected from Fas-mediated killing relative to wild type T cells. Thus CD47 associates with Fas upon its activation and augments Fas-mediated apoptosis.

Received for publication, January 25, 2005 , and in revised form, May 10, 2005.

^* This work was supported by Grants GM57573 (to W. A. F. and P.-A. O.) and HL54390 (to W. A. F.) from the National Institutes of Health, Grants 06P-14098 and 31X-14286 from the Swedish Research Council, and by grants from the Swedish Society of Medicine, the Åke Wiberg Foundation, and the Faculty of Medicine, Umeå University (to P.-A. O.). 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: Dept. of Biochemistry and Molecular Biophysics, Washington University School of Medicine, Box 8231, 660 S. Euclid Ave., St. Louis, MO 63110. Tel.: 314-362-3349; Fax: 314-362-7183; E-mail: frazier{at}biochem.wustl.edu.

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