title: Reduction of Runx1 transcription factor activity up-regulates Fas and Bim expression and enhances the apoptotic sensitivity of double positive thymocytes.
abstract: The death or survival of double positive (DP) thymocytes is determined by the strength of their TCR signaling. Of the three Runx family proteins, the DP cells only express the Runx1 transcription factor. We introduced and expressed in murine thymocytes the Runt domain of Runx1, which antagonizes the activity of endogenous Runx1. The Runt transgenic DP thymocytes expressed higher levels of the proapoptotic molecules Fas and Bim compared with the wild-type cells. Furthermore, the Runt transgenic cells were more susceptible to apoptosis induced by the artificial cross-linking of the TCR by the anti-CD3 Ab. This susceptibility was partially abrogated by the lpr/lpr background. In addition, Runx1:HY-TCR-double transgenic DP thymocytes were resistant to the apoptosis induced by the endogenously presented HY Ag. We propose that Runx1 functions to suppress the apoptotic sensitivity of DP thymocytes in the context of TCR signaling.
authors.affiliation: Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Abe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kohu
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Ohmori
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Katsuto
authors.initials: K
authors.lastname: Hozumi
authors.forename: Takehito
authors.initials: T
authors.lastname: Sato
authors.forename: Sonoko
authors.initials: S
authors.lastname: Habu
authors.forename: Masanobu
authors.initials: M
authors.lastname: Satake
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D015704:CD4 Antigens / Q000096:biosynthesis*; D016827:CD8 Antigens / Q000096:biosynthesis*; D006182:H-Y Antigen / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*; D019014:fas Receptor
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D015704:CD4 Antigens; D016827:CD8 Antigens; C491899:Fas protein, mouse; D006182:H-Y Antigen; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor