Park H
Department of Life Science, University of Seoul, Korea.
Mol Cells. 1999 Apr 30;9(2):172-8.
Aromatic hydrocarbon nuclear translocator (Arnt) is an ubiquitously expressed protein that contains basic helix-loop-helix (bHLH) and Per-AhR-Arnt-Sim (PAS) motifs. Other bHLH-PAS proteins, hypoxia-inducible factor-1alpha (HIF-1alpha) and aromatic hydrocarbon receptor (AhR) mediate hypoxia- and dioxin-signal pathway, respectively. Arnt has been identified as a heterodimerization partner for AhR. AhR/Arnt heterodimer binds the regulatory region of xenobiotic-induced genes and activates their transcription. Here, in vivo results provide evidence that Arnt is involved in not only xenobiotic- but also hypoxia-induced transcriptional activation. In hypoxic condition, Arnt dimerizes with HIF-1alpha to make HIF-1alpha/Arnt heterodimer which is able to bind hypoxia-responsive DNA elements. The HIF-1alpha/Arnt heterodimer functions as a transactivator for hypoxia-inducible genes. Given that the expression of Arnt is limited, HIF-1alpha may compete with AhR for recruiting Arnt as a heteromeric partner. Consistent with this idea, the results indicate that the hypoxic activation of HIF-1alpha reduces dioxin-induced AhR's function on the dioxin-responsive reporter gene and the endogenous gene.
芳烃核转运蛋白（Arnt）是一种广泛表达的蛋白质，含有碱性螺旋-环-螺旋（bHLH）和Per-AhR-Arnt-Sim（PAS）基序。其他bHLH-PAS蛋白，即缺氧诱导因子-1α（HIF-1α）和芳烃受体（AhR），分别介导缺氧信号通路和二噁英信号通路。Arnt已被确定为AhR的异源二聚化伴侣。AhR/Arnt异源二聚体结合外源性诱导基因的调控区域并激活其转录。在此，体内实验结果表明，Arnt不仅参与外源性物质诱导的转录激活，还参与缺氧诱导的转录激活。在缺氧条件下，Arnt与HIF-1α二聚化形成HIF-1α/Arnt异源二聚体，该异源二聚体能够结合缺氧反应性DNA元件。HIF-1α/Arnt异源二聚体作为缺氧诱导基因的反式激活因子发挥作用。鉴于Arnt的表达有限，HIF-1α可能会与AhR竞争招募Arnt作为异源伴侣。与这一观点一致的是，结果表明HIF-1α的缺氧激活降低了二噁英诱导的AhR对二噁英反应性报告基因和内源性基因的作用。
