Modulation of transforming growth factor beta signalling pathway genes by transforming growth factor beta in human osteoarthritic chondrocytes: involvement of Sp1 in both early and late response cells to transforming growth factor beta

The transforming growth factor-β (TGFβ) type II receptor (TβR-II) is responsible for transducing the growth inhibitory signals of TGFβ. The TβR-II gene promoter lacks both a TATA box and a CAAT box near the transcription initiation site, and has been shown to contain binding sequences for several tr...

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Veröffentlicht in:Arthritis research & therapy 2010-11, Vol.13 (1)
Hauptverfasser: Baugé, Catherine, Cauvard, Olivier, Leclercq, Sylvain, Galéra, Philippe, Boumédiene, Karim
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Sprache:eng
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Zusammenfassung:The transforming growth factor-β (TGFβ) type II receptor (TβR-II) is responsible for transducing the growth inhibitory signals of TGFβ. The TβR-II gene promoter lacks both a TATA box and a CAAT box near the transcription initiation site, and has been shown to contain binding sequences for several transcription factors (Sp1, AP1, NF-Y, Cut and ERT) which are important for TβR-II gene promoter activity in vitro. However, it is still not clear which interactions are important for the regulation of TβR-II gene promoter activity in vivo. Using in vivo genomic DNA footprinting of normal human epithelial cells (HaCaT), we have identified two novel identical and strongly protected sites (ggggctgg) at positions −59 and −102 of the TβR-II gene promoter. Mutation of either site significantly reduced promoter activity in transient transfections. Protein binding to these sites, as determined by electrophoretic mobility shift assays (EMSA), was specifically competed with consensus Sp1 oligonucleotides. Furthermore, anti-Sp1/3 antibodies produced band shifts when incubated with the TβR-II −59 and −102 DNA probes. Importantly, Sp1 protein binding was influenced by the presence of an intact NF-Y binding site at position −83. Our data suggests that both Sp1 and NF-Y may play an important role in regulating TβR-II gene promoter basal activity in vivo.
ISSN:1478-6354
DOI:10.1038/sj.onc.1204808