KMID : 0578320070240020283
|
|
Molecules and Cells 2007 Volume.24 No. 2 p.283 ~ p.287
|
|
Opposing Effects of Arkadia and Smurf on TGF¥â1-induced IgA Isotype Expression
|
|
Choi Seo-Hyun
Seo Goo-Young Nam Eun-Hee Jeon Seong-Hyun Kim Hyun-A Park Jae-Bong Kim Pyeung-Hyeun
|
|
Abstract
|
|
|
TGF-¥â1 induces Ig germ-line ¥á (GL¥á) 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¥â1-induced IgA CSR. We found that over-expression of Smurf1 and Smurf2 decreased TGF¥â1-induced GL¥á 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¥á promoter activities, suggesting that the Smurfs can down-regulate the major TGF-¥â1 signaling pathway and decrease GL¥á gene expression. In parallel, the over-expressed Smurf1 decreased the expression of endogenous IgA CSR-predictive transcripts (GLT¥á, PST¥á, and CT¥á) and also TGF¥â?1-induced IgA secretion. Conversely over-expression of Arkadia abolished the inhibitory effect of Smad7 on TGF¥â1-induced GLT? 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¥â1-induced IgA CSR by degrading Smad7, which interacts with Smurf1. We conclude that Smurf and Arkadia have opposite roles in the regulation of TGF¥â1-induced IgA isotype expression.
|
|
KEYWORD
|
|
Arkadia, IgA, Smad7, Smurf, TGF-¥â1
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|