title: A novel gene product that couples TCR signaling to Fas(CD95) expression in activation-induced cell death.
abstract: Cross-linking the TCR in T cell hybridomas induces cell apoptosis following activation. This activation-induced apoptosis has been used as a model for clonal deletion of thymocytes or peripheral T cells. Anti-TCR-induced apoptosis of T cell hybridomas requires de novo macromolecular synthesis, including up-regulation of Fas and FasL. The Fas-FasL interaction then activates the apoptosis program. To study apoptosis-specific signaling processes, we generated a mutant T cell hybridoma line defective in induction of apoptosis, but competent to induce activation, upon TCR triggering. Subsequently, we cloned the gene TDAG51, which restored activation-induced apoptosis when transfected into the mutant cell line, and showed that TDAG51 expression was required for Fas expression. Thus, TDAG51 plays an essential role in induction of apoptosis by coupling TCR stimulation to Fas expression.
authors.affiliation: Howard Hughes Medical Institute, Rockefeller University, New York 10021, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Park
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.forename: G
authors.initials: G
authors.lastname: Kandala
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000235:genetics* / Q000276:immunology*; D002469:Cell Separation; D003001:Cloning, Molecular; D006825:Hybridomas; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: C114072:Phlda1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D019014:fas Receptor