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KMID : 0923620090090060248
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Immune Network
2009 Volume.9 No. 6 p.248 ~ p.254
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Tiul1 and TGIF are Involved in Downregulation of TGF?1-induced IgA Isotype Expression
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Park Kyoung-Hoon
Nam Eun-Hee
Seo Goo-Young
Seo Su-Ryeon
Kim Pyeung-Hyeun
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Abstract
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TGF-?1 is well known to induce Ig germ-line ? (GL?) 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-? signaling. In the present study, we investigated the roles of Tiul1 and TGIF in TGF?1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGF?1-induced GL? promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GL? promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGF?1- induced GL? expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLT?, PST?, and CT?) and TGF?1-induced IgA secretion, but not GLT?3 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?1-induced IgA isotype expression.
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KEYWORD
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TGF-?1, Tiul1, TGIF, IgA, T?RI, Smad
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