Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea.
Immune Netw. 2009 Dec;9(6):248-54. doi: 10.4110/in.2009.9.6.248. Epub 2009 Dec 31.
TGF-beta1 is well known to induce Ig germ-line alpha (GLalpha) 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 TGFbeta1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGFbeta1-induced GLalpha promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GLalpha promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFbeta1-induced GLalpha expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLT(alpha), PST(alpha), and CT(alpha)) and TGFbeta1-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 TGFbeta1-induced IgA isotype expression.
转化生长因子-β1（TGF-β1）被广泛认为可诱导免疫球蛋白重链基因（GLalpha）转录，并随后诱导 IgA 同种型类别转换重组（CSR）。同源盒蛋白 TG 相互作用因子（TGIF）和 E3 泛素连接酶 TGIF 相互作用泛素连接酶 1（Tiul1）被认为参与 TGF-β信号的负调控。在本研究中，我们研究了 Tiul1 和 TGIF 在 TGFβ1 诱导的 IgA CSR 中的作用。我们发现，Tiul1 的过表达降低了 TGFβ1 诱导的 GLalpha 启动子活性，并增强了 Smad7 对启动子活性的抑制作用。同样，TGIF 的过表达也降低了 GLalpha 启动子活性，并进一步增强了 Tiul1 的抑制作用，表明 Tiul1 和 TGIF 可以下调 TGFβ1 诱导的 GLalpha 表达。同时，Tiul1 的过表达降低了内源性 IgA CSR 预测性转录物（GLT(alpha)、PST(alpha)和 CT(alpha))和 TGFβ1 诱导的 IgA 分泌，但不影响 GLT(gamma3)和 IgG3 的分泌。在此，过表达的 TGIF 进一步加强了 Tiul1 的抑制作用。这些结果表明，Tiul1 和 TGIF 作为 TGFβ1 诱导的 IgA 同种型表达的负调控因子发挥作用。
