title: CD47 augments Fas/CD95-mediated apoptosis.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Partha P
authors.initials: PP
authors.lastname: Manna
authors.forename: Julie
authors.initials: J
authors.lastname: Dimitry
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
authors.forename: William A
authors.initials: WA
authors.lastname: Frazier
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis; D051928:CD47 Antigen; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D019014:fas Receptor / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; C497895:Cd47 protein, mouse; D019014:fas Receptor