The Smad3 linker region contains a transcriptional activation domain.
The Smad3 linker region contains a transcriptional activation domain.
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DOI：
10.1042/bj20041820
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发表时间：
2005-02
期刊：
影响因子：
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通讯作者：
Guannan Wang;Jianyin Long;I. Matsuura;Dongming He;Fang Liu
中科院分区：
文献类型：
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作者：
Guannan Wang;Jianyin Long;I. Matsuura;Dongming He;Fang Liu
转化生长因子-β（TGF-β）/Smads通过靶基因的转录调节来调节多种生物反应。Smad 3在TGF-β/Smad介导的转录应答中起关键作用。在这里，我们表明，富含脯氨酸的Smad 3连接区包含一个转录激活结构域。当接头区与异源DNA结合结构域融合时，它激活转录。我们表明，连接区与p300的物理相互作用。与p300结合的腺病毒E1 a蛋白抑制接头区的转录活性，并且p300的过表达可以挽救接头介导的转录激活。相反，不能与p300结合的腺病毒E1 a突变体不抑制接头介导的转录。缺乏接头区的天然Smad 3蛋白不能介导TGF-β转录激活反应，尽管它可以被TGF-β受体在C-末端尾磷酸化，并且具有显著增加的与Smad 4形成异聚复合物的能力。我们进一步表明，在TGF-β的存在下，Smad 3的连接区和C-末端结构域协同转录激活。因此，我们的研究结果揭示了一个重要的功能，Smad 3连接区在Smad介导的转录控制。
Transforming growth factor-beta (TGF-beta)/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Smad3 plays a key role in TGF-beta/Smad-mediated transcriptional responses. Here, we show that the proline-rich linker region of Smad3 contains a transcriptional activation domain. When the linker region is fused to a heterologous DNA-binding domain, it activates transcription. We show that the linker region physically interacts with p300. The adenovirus E1a protein, which binds to p300, inhibits the transcriptional activity of the linker region, and overexpression of p300 can rescue the linker-mediated transcriptional activation. In contrast, an adenovirus E1a mutant, which cannot bind to p300, does not inhibit the linker-mediated transcription. The native Smad3 protein lacking the linker region is unable to mediate TGF-beta transcriptional activation responses, although it can be phosphorylated by the TGF-beta receptor at the C-terminal tail and has a significantly increased ability to form a heteromeric complex with Smad4. We show further that the linker region and the C-terminal domain of Smad3 synergize for transcriptional activation in the presence of TGF-beta. Thus our findings uncover an important function of the Smad3 linker region in Smad-mediated transcriptional control.