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Tiul1 and TGIF are Involved in Downregulation of $TGF{\beta}1$-induced IgA Isotype Expression

  • Park, Kyoung-Hoon (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University) ;
  • Nam, Eun-Hee (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University) ;
  • Seo, Goo-Young (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University) ;
  • Seo, Su-Ryeon (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University) ;
  • Kim, Pyeung-Hyeun (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University)
  • Received : 2009.11.24
  • Accepted : 2009.12.09
  • Published : 2009.12.31
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Abstract

[ $TGF-{\beta}1$ ]is well known to induce Ig germ-line ${\alpha}$ ($GL{\alpha}$) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of $TGF-{\beta}$ signaling. In the present study, we investigated the roles of Tiul1 and TGIF in $TGF{\beta}1$-induced IgA CSR. We found that over-expression of Tiul1 decreased $TGF{\beta}1$-induced $GL{\alpha}$ promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished $GL{\alpha}$ promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate $TGF{\beta}1$-induced $GL{\alpha}$ expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts ($GLT_{\alpha},\;PST_{\alpha},\;and\;CT_{\alpha}$) and $TGF{\beta}1$-induced IgA secretion, but not $GLT_{\gamma3}$ and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in $TGF{\beta}1$-induced IgA isotype expression.

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References

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