CBP/p300 functions as a possible transcriptional coactivator of Ah receptor nuclear translocator (Arnt).
CBP/p300 functions as a possible transcriptional coactivator of Ah receptor nuclear translocator (Arnt).
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DOI：
10.1093/oxfordjournals.jbchem.a021812
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发表时间：
1997-10
影响因子：
2.7
通讯作者：
Akira Kobayashi;K. Numayama‐Tsuruta;K. Sogawa;Y. Fujii‐Kuriyama
中科院分区：
文献类型：
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作者：
Akira Kobayashi;K. Numayama‐Tsuruta;K. Sogawa;Y. Fujii‐Kuriyama
AhR（芳香烃受体）和Arnt（AhR核转运蛋白）的异源二聚体将芳香烃如2，3，7，8-四氯二苯并-p-二恶英和3-甲基胆蒽的反式激活信号传递给一组药物代谢酶的基因。腺病毒E1 A可抑制基因的诱导表达，表明CBP/p300在某种程度上参与了AhR和Arnt异源二聚体对基因的反式激活。酵母和哺乳动物双杂交系统表明CBP/p300通过CREB结合结构域与Arnt的反式激活结构域相互作用，而与AhR的反式激活结构域不相互作用。使用GST-Arnt杂合蛋白的pull down试验证实了Arnt与CBP/p300之间的相互作用。考虑到这些结果以及Arnt或Arnt 2在与其他bHLH/PAS蛋白如AhR、HLF和HIF-1 α形成转录调节因子中作为共同伴侣起作用，CBP/p300可能作为共激活因子广泛参与bHLH/PAS的反式激活过程（Per、Arnt和Sim之间的保守序列基序）异二聚体转录因子通过与Arnt或Arnt 2相互作用。
A heterodimer of AhR (aryl hydrocarbon receptor) and Arnt (AhR nuclear translocator) conveys a transactivation signal of aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene to the genes for a group of drug-metabolizing enzymes. This inducible expression of the genes is inhibited by adenovirus E1A, suggesting that CBP/p300 is somehow involved in the transactivation of the genes by the AhR and Arnt heterodimer. Yeast and mammalian two hybrid systems revealed that CBP/p300 interacted with the transactivation domain of Arnt, but not with that of AhR, via the CREB-binding domain. The pull down assay using GST-Arnt hybrid protein confirmed the interaction between Arnt and CBP/p300. Considering these results and that Arnt or Arnt2 functions as a common partner in the formation of transcriptional regulators with other bHLH/PAS proteins such as AhR, HLF, and HIF-1alpha, the possibility arises that CBP/p300 is extensively involved as a coactivator in the transactivation process by bHLH/PAS (a conserved sequence motif among Per, Arnt, and Sim) heterodimer transcription factors through interaction with Arnt or Arnt2.