title: Daxx plays a novel role in T cell survival but is dispensable in Fas-induced apoptosis.
abstract: Daxx was originally isolated as a Fas-binding protein. However, the in vivo function of Daxx in Fas-induced apoptosis has remained enigmatic. Fas plays an important role in homeostasis in the immune system. Fas gene mutations lead to autoimmune-lymphoproliferation (lpr) diseases characterized by hyperplasia of secondary lymphoid organs. It is well established that the FADD adaptor binds to Fas, and recruits/activates caspase 8. However, additional proteins including Daxx have also been indicated to associate with Fas. It was proposed that Daxx mediates a parallel apoptotic pathway that is independent of FADD and caspase 8, but signals through ASK1-mediated apoptotic pathway. However, because the deletion of Daxx leads to embryonic lethality, the in vivo function of Daxx has not been properly analyzed. In the current study, analysis was performed using a conditional mutant mouse in which Daxx was deleted specifically in T cells. The data show that Daxx-/- T cells were able to undergo normal Fas-induced apoptosis. While containing normal thymocyte populations, the T cell-specific Daxx-/- mice have a reduced peripheral T cell pool. Importantly, Daxx-deficient T cells displayed increased death responses upon activation through TCR stimulation. These results unequivocally demonstrated that Daxx does not mediate Fas-induced apoptosis, but rather that it plays a critical role in survival responses in primary mature T cells.
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Liangyue
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: Dowling
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Curcione
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Drishya
authors.initials: D
authors.lastname: Kurup
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.|Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jianke
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D056970:Co-Repressor Proteins; D005434:Flow Cytometry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D019014:fas Receptor