Negative regulation of transcription coactivator p300 by orphan receptor TR3.
Negative regulation of transcription coactivator p300 by orphan receptor TR3.
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孤儿受体 TR3 对转录辅激活因子 p300 的负调控
DOI：
10.1093/nar/gkm870
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发表时间：
2007
影响因子：
14.9
通讯作者：
Wu, Qiao
中科院分区：
文献类型：
--
作者：
Li, Gui-Deng;Fang, Jin-Xu;Chen, Hang-Zi;Luo, Jie;Zheng, Zhong-Hui;Shen, Yue-Mao;Wu, Qiao
P300通过形成激活复合物和/或促进组蛋白乙酰化调节多种转录因子的转录活性。在这里，我们发现孤儿受体TR3在负向调节p300功能方面具有独特的特性。TR3与p300相互作用，抑制p300诱导的转录因子乙酰化，抑制其转录活性。进一步分析表明，p300中的保守转录适配器基序（TRAM）和TR3中的特定序列FLELFIL对它们的相互作用至关重要。TR3的结合完全覆盖了p300的组蛋白乙酰转移酶（histone acetyltransferase， HAT）结构域，导致HAT活性受到抑制，因为p300诱导的组蛋白H3乙酰化和转录被TR3的存在所抑制。此外，从内生真菌dothiiorella sp. HTF3中分离的天然octaketide TR3的激动剂被证明是一种有效抑制p300 HAT活性的化合物（IC50 = 1.5 μg/ml）。更重要的是，这种激动剂可以抑制转录因子的转录活性，抑制癌细胞的增殖。综上所述，我们的研究结果不仅描绘了TR3的一种新的转录抑制因子功能，而且揭示了其对p300 HAT活性的调节是潜在的机制。
p300 regulates the transcriptional activity of a variety of transcription factors by forming an activation complex and/or promoting histone acetylation. Here, we show a unique characteristic of orphan receptor TR3 in negatively regulating the function of p300. TR3 was found to interact with p300 and inhibited the acetylation of transcription factors induced by p300, resulting in the repression of their transcriptional activity. Further analysis revealed that both a conserved transcriptional adapter motif (TRAM) in p300 and a specific sequence FLELFIL in TR3 were critical for their interaction. TR3 binding completely covered the histone acetyltransferase (HAT) domain of p300 and resulted in suppression of the HAT activity, as the p300-induced histone H3 acetylation and transcription were inhibited with the presence TR3. Furthermore, an agonist of TR3, a natural octaketide isolated from Dothiorella sp. HTF3 of an endophytical fungus, was shown to be a potent compound for inhibiting p300 HAT activity (IC50 = 1.5 μg/ml) in vivo. More importantly, this agonist could repress the transcriptional activity of transcription factors, and proliferation of cancer cells. Taken together, our results not only delineate a novel transcriptional repressor function for TR3, but also reveal its modulation on p300 HAT activity as the underlying mechanism.
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影响因子：
15.3
作者：
Ito, Kazuhiro;Yamamura, Satoshi;Essilfie-Quaye, Sarah;Cosio, Borja;Ito, Misako;Barnes, Peter J;Adcock, Ian M
通讯作者：
Adcock, Ian M
影响因子：
64.5
作者：
Chakravarti, D;Ogryzko, V;Evans, RM
通讯作者：
Evans, RM
影响因子：
5.3
作者：
Huang, WC;Chen, CC
通讯作者：
Chen, CC
DOI：
10.1073/pnas.96.20.11566
发表时间：
1999-09-28
影响因子：
11.1
作者：
Jayachandra, S;Low, KG;Moore, PS
通讯作者：
Moore, PS
影响因子：
5.3
作者：
Lévy, L;Wei, Y;Neuveut, C
通讯作者：
Neuveut, C