A repressor of GATA-mediated negative feedback mechanism of T cell activation.
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.
Miaw
Shi-Chuen
SC
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kang
Bok Yun
BY
White
Ian Alexander
IA
Ho
I-Cheng
IC
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
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