title: The CD23b promoter is a target for NF-AT transcription factors in B-CLL cells.
abstract: CD23 is atypically highly expressed in various chronic diseases, including B-CLL, lupus erythematodes and rheumatoid arthritis. Its expression can be further enhanced by interleukin 4 (IL-4). We have shown before that in B-CLL cells nuclear factor(s) of activated T cells (NF-ATs) show permanent nuclear localization and therefore constitutive transcriptional activity. Here we identify CD23b promoter as a novel target for NF-AT factors in B-CLL cells. The CD23b promoter contains two NF-AT binding sites to which NF-ATp and NF-ATc factors bind with high affinity. Mutations introduced into these sites abolished NF-AT binding and impaired the promoter activity, as did cyclosporin A (CsA), an inhibitor of nuclear transport of NF-ATs. Furthermore, we show that IL-4-induced transcription factor STAT6 cooperates with NF-ATs in the induction of the CD23b promoter activity. These results show that the CD23b promoter is a target for NF-AT factors and suggest that the cooperation between NF-AT and STAT factors might be one of the molecular mechanisms responsible for high-level expression of CD23 on the surface of B-CLL cells.
authors.affiliation: Medizinische Poliklinik, University of Wuerzburg, Klinikstrasse. 6-8, 97070, Wuerzburg, Germany. c.kneitz@medizin.uni-wuerzburg.de
authors.forename: Christian
authors.initials: C
authors.lastname: Kneitz
authors.forename: Martin
authors.initials: M
authors.lastname: Goller
authors.forename: Hans
authors.initials: H
authors.lastname: Tony
authors.forename: Andreas
authors.initials: A
authors.lastname: Simon
authors.forename: Corinne
authors.initials: C
authors.lastname: Stibbe
authors.forename: Thomas
authors.initials: T
authors.lastname: König
authors.forename: Edgar
authors.initials: E
authors.lastname: Serfling
authors.forename: Andris
authors.initials: A
authors.lastname: Avots
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D015759:Ionomycin; D015448:Leukemia, B-Cell / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics*; D050800:STAT6 Transcription Factor; D013755:Tetradecanoylphorbol Acetate; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017455:Receptors, IgE; D050800:STAT6 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D015759:Ionomycin; D004247:DNA; D013755:Tetradecanoylphorbol Acetate