Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Opposing Effects of Arkadia and Smurf on TGFβ1-induced IgA Isotype Expression

  • Choi, Seo-Hyun (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) ;
  • Nam, Eun-Hee (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University) ;
  • Jeon, Seong-Hyun (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University) ;
  • Kim, Hyun-A (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University) ;
  • Park, Jae-Bong (Department of Biochemistry, College of Medicine, Hallym University) ;
  • Kim, Pyeung-Hyeun (Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University)
  • Received : 2007.05.11
  • Accepted : 2007.05.28
  • Published : 2007.10.31
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Abstract

$TGF-{\beta}1$ induces Ig germ-line ${\alpha}$ ($GL{\alpha}$) transcription and subsequent class switching recombination (CSR) to IgA. In the present study, we investigated the roles of two E3-ubiquitin ligases, Smurfs (HECT type) and Arkadia (RING finger type) on $TGF{\beta}1$-induced IgA CSR. We found that over-expression of Smurf1 and Smurf2 decreased $TGF{\beta}1$-induced $GL{\alpha}$ promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Further, over-expression of Smurf1 and Smurf2 decreased both Smad3/4-mediated and Runx3-mediated $GL{\alpha}$ promoter activities, suggesting that the Smurfs can down-regulate the major $TGF-{\beta}1$ signaling pathway and decrease $GL{\alpha}$ gene expression. In parallel, the over-expressed Smurf1 decreased the expression of endogenous IgA CSR-predictive transcripts ($GLT_{\alpha}$, $PST_{\alpha}$, and $CT_{\alpha}$) and also $TGF{\beta}1$-induced IgA secretion. Conversely over-expression of Arkadia abolished the inhibitory effect of Smad7 on $TGF{\beta}1$-induced $GLT_{\alpha}$ expression and IgA secretion. Similar results were obtained in the presence of over-expressed Smad7 and Smurf1. These results indicate that Arkadia can amplify $TGF{\beta}1$-induced IgA CSR by degrading Smad7, which interacts with Smurf1. We conclude that Smurf and Arkadia have opposite roles in the regulation of $TGF{\beta}1$-induced IgA isotype expression.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

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