Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA.
Cancer Lett. 2012 Jul 1;320(1):111-21. doi: 10.1016/j.canlet.2012.01.037. Epub 2012 Feb 2.
The aryl hydrocarbon receptor nuclear translocator (ARNT) heterodimerizes with hypoxia inducible factor-1α (HIF-1α), followed by upregulation of genes that are essential for carcinogenesis. We utilized a novel peptide (Ainp1) to address whether the HIF-1α signaling could be suppressed by an ARNT-mediated mechanism. Ainp1 suppresses the HIF-1α-dependent luciferase expression in Hep3B cells and this suppression can be reversed by ARNT. Ainp1 reduces the interaction between ARNT and HIF-1α, suppresses the formation of the HIF-1 gel shift complex, and suppresses the ARNT recruitment to the vegf promoter. These effects are partly mediated by redistribution of the nuclear ARNT contents to the cytoplasm.
芳香烃受体核转位蛋白（ARNT）与缺氧诱导因子-1α（HIF-1α）形成异二聚体，随后上调致癌基因。我们利用一种新型肽（Ainp1）来确定 HIF-1α 信号是否可以通过 ARNT 介导的机制受到抑制。Ainp1 抑制 Hep3B 细胞中 HIF-1α 依赖性荧光素酶表达，而这种抑制作用可以被 ARNT 逆转。Ainp1 减少了 ARNT 和 HIF-1α 之间的相互作用，抑制了 HIF-1 凝胶迁移复合物的形成，并抑制了 ARNT 募集到 vegf 启动子。这些作用部分是通过将核 ARNT 含量重新分配到细胞质中来介导的。
