title: The IFN regulatory factor family participates in regulation of Fas ligand gene expression in T cells.
abstract: TCR engagement leads to the transcriptional activation of cytokine genes and activation-induced cell death. Activated T cells undergo apoptosis upon expression and ligation of Fas ligand (FasL) to Fas/APO-1 (CD95) receptor. FasL expression is under the transcriptional regulation of multiple factors. The present study demonstrates that TCR-inducible FasL expression is also under the direct influence of the IFN regulatory factor (IRF) transcription factor family. Deletion and mutagenesis of a putative IRF-1 binding site in the FasL promoter results in deficient expression of FasL. EMSAs demonstrate specific FasL promoter binding by IRF-1 and IRF-2. Forced expression of either IRF-1 or IRF-2 leads to FasL promoter activation in T cells and FasL expression in heterologous cells. Finally, suppression of IRF-1 expression in T cells results in deficient TCR-induced FasL expression. These results confirm that the IRF family participates in the regulation of FasL gene expression.
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA. wchow@coh.org
authors.forename: W A
authors.initials: WA
authors.lastname: Chow
authors.forename: J J
authors.initials: JJ
authors.lastname: Fang
authors.forename: J K
authors.initials: JK
authors.lastname: Yee
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma / Q000502:physiology*; D019169:Jurkat Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D005810:Multigene Family / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000276:immunology; D012097:Repressor Proteins; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D007371:Interferon-gamma