title: NFATc3 regulates the transcription of genes involved in T-cell activation and angiogenesis.
abstract: The nuclear factor of activated T cells (NFAT) family of transcription factors plays important roles in many biologic processes, including the development and function of the immune and vascular systems. Cells usually express more than one NFAT member, raising the question of whether NFATs play overlapping roles or if each member has selective functions. Using mRNA knock-down, we show that NFATc3 is specifically required for IL2 and cyclooxygenase-2 (COX2) gene expression in transformed and primary T cells and for T-cell proliferation. We also show that NFATc3 regulates COX2 in endothelial cells, where it is required for COX2, dependent migration and angiogenesis in vivo. These results indicate that individual NFAT members mediate specific functions through the differential regulation of the transcription of target genes. These effects, observed on short-term suppression by mRNA knock-down, are likely to have been masked by compensatory effects in gene-knockout studies.
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Katia
authors.initials: K
authors.lastname: Urso
authors.forename: Arantzazu
authors.initials: A
authors.lastname: Alfranca
authors.forename: Sara
authors.initials: S
authors.lastname: Martínez-Martínez
authors.forename: Amelia
authors.initials: A
authors.lastname: Escolano
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ortega
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Redondo
mesh_terms: D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D007376:Interleukin-2; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C494008:NFATC3 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human