Role of p300, a transcriptional coactivator, in signalling of TGF-β
Role of p300, a transcriptional coactivator, in signalling of TGF-β
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DOI：
10.1046/j.1365-2443.1998.00217.x
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发表时间：
1998-09-01
期刊：
影响因子：
2.1
通讯作者：
Kawabata, M
中科院分区：
文献类型：
--
作者：
Nishihara, A;Hanai, J;Kawabata, M
背景：Smad蛋白是介导转化生长因子- β (tgf - β)超家族信号传导的新型转录调控因子，p300/CBP等共激活因子通过与各种转录因子的直接相互作用促进其反激活。结合p300的腺病毒癌蛋白E1A被证明可以抑制tgf - β的信号传导，这些发现提出了p300可能参与tgf - β信号传导的可能性。结果：我们研究了p300是否参与smad的转激活，p300增强smad诱导的p3TP-Lux （tgf - β应答报告基因）的转激活，E1A抑制这种增强，抑制需要其结合p300/CBP的能力。p300和Smad3以及Smad2在体内以配体依赖的方式相互作用。Smad3的结合区域是它的c端一半，之前已经证明它具有内在的交易激活活性。p300的结合区定位到其c端678个氨基酸。最小的smad2 /3相互作用区域以及p300的其余部分以显性负向方式抑制p3TP-Lux的转激活。结论：p300以配体依赖的方式与Smad2和Smad3相互作用，并增强Smad的反活化作用，为Smad蛋白反活化提供了分子基础。
Background: Smad proteins are novel transcriptional regulators mediating the signalling of the transforming growth factor-beta (TGF-beta) superfamily, Coactivators such as p300/CBP promote transactivation by various transcription factors through a direct interaction with them. Adenoviral oncoprotein E1A, which binds p300, was shown to inhibit the signalling of TGF-beta, These findings raise the possibility that p300 may be involved in TGF-beta signalling.Results: We investigated whether p300 is involved in transactivation by Smads, p300 enhanced the Smad-induced transactivation of p3TP-Lux, a TGF-beta responsive reporter, E1A inhibited this enhancement, and the inhibition required its ability to bind p300/CBP. p300 and Smad3, as well as Smad2, interacted in vivo in a Ligand-dependent manner. The binding region in Smad3 was its C-terminal half that was previously shown to possess an intrinsic transactivation activity. The binding region in p300 was mapped to its C-terminal 678 amino acids. The minimal Smad2/3-interacting region, as well as the rest of the p300, inhibited the transactivation of p3TP-Lux in a dominant-negative fashion.Conclusion: p300 interacted with Smad2 and Smad3 in a ligand-dependent manner, and enhanced the transactivation by Smads, Our results present the molecular basis of the transactivation by Smad proteins.