title: A repressor of GATA-mediated negative feedback mechanism of T cell activation.
abstract: The NF-AT family is a group of potent transcription factors that are essential for T cell activation in vitro. However, NF-ATc2-deficient Th cells display hyperproliferation in response to stimulation, suggesting that NF-ATc2 functions as a negative regulator of Th cell activation/proliferation. In this study we show that the transcriptional repressor of GATA (ROG) is a direct target gene of NF-ATc2 and that NF-ATc2-deficient Th cells are unable to fully up-regulate ROG upon stimulation. Restoration of ROG expression in vivo partly corrects the hyperproliferation of NF-ATc2-deficient Th cells by attenuating TCR signals. Our data, therefore, depict a ROG-mediated negative feedback mechanism of T cell activation.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shi-Chuen
authors.initials: SC
authors.lastname: Miaw
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
authors.forename: Ian Alexander
authors.initials: IA
authors.lastname: White
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Ho
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D025461:Feedback, Physiological / Q000235:genetics / Q000276:immunology*; D050990:GATA3 Transcription Factor; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; C406863:Rog protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors