Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718, Korea.
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon 200-701, Korea.
Immune Netw. 2014 Dec;14(6):321-7. doi: 10.4110/in.2014.14.6.321. Epub 2014 Dec 22.
TGF-β induces IgA class switching by B cells. We previously reported that Smad3 and Smad4, pivotal TGF-β signal-transducing transcription factors, mediate germline (GL) α transcription induced by TGF-β1, resulting in IgA switching by mouse B cells. Post-translational sumoylation of Smad3 and Smad4 regulates TGF-β-induced transcriptional activation in certain cell types. In the present study, we investigated the effect of sumoylation on TGF-β1-induced, Smad3/4-mediated GLα transcription and IgA switching by mouse B cell line, CH12F3-2A. Overexpression of small ubiquitin-like modifier (SUMO)-1, SUMO-2 or SUMO-3 did not affect TGF-β1-induced, Smad3/4-mediated GLα promoter activity, expression of endogenous GLα transcripts, surface IgA expression, and IgA production. Next, we tested the effect of the E3 ligase PIASy on TGF-β1-induced, Smad3/4-mediated GLα promoter activity. We found that PIASy overexpression suppresses the GLα promoter activity in cooperation with histone deacetylase 1. Taken together, these results suggest that SUMO itself does not affect regulation of GLα transcription and IgA switching induced by TGF-β1/Smad3/4, while PIASy acts as a repressor.
TGF-β 通过 B 细胞诱导 IgA 类别转换。我们之前曾报道过，TGF-β 信号转导的关键转录因子 Smad3 和 Smad4 介导由 TGF-β1 诱导的种系 (GL)α 转录，从而导致小鼠 B 细胞发生 IgA 转换。Smad3 和 Smad4 的翻译后 SUMO 化调节某些细胞类型中 TGF-β 诱导的转录激活。在本研究中，我们研究了 SUMO 化对 TGF-β1 诱导的、Smad3/4 介导的 GLα 转录和小鼠 B 细胞系 CH12F3-2A 中 IgA 转换的影响。小泛素样修饰物 (SUMO)-1、SUMO-2 或 SUMO-3 的过表达不会影响 TGF-β1 诱导的、Smad3/4 介导的 GLα 启动子活性、内源性 GLα 转录本的表达、表面 IgA 表达和 IgA 产生。接下来，我们测试了 E3 连接酶 PIASy 对 TGF-β1 诱导的、Smad3/4 介导的 GLα 启动子活性的影响。我们发现，PIASy 的过表达与组蛋白去乙酰化酶 1 协同抑制 GLα 启动子活性。总之，这些结果表明 SUMO 本身不会影响 TGF-β1/Smad3/4 诱导的 GLα 转录和 IgA 转换的调节，而 PIASy 作为一种抑制剂发挥作用。
