Venugopal R, Jaiswal A K
Department of Pharmacology, Baylor College of Medicine, Texas 77030-3498, USA.
Oncogene. 1998 Dec 17;17(24):3145-56. doi: 10.1038/sj.onc.1202237.
Antioxidant response element (ARE)-mediated expression and coordinated induction of genes encoding detoxifying enzymes is one mechanism of critical importance to cellular protection against oxidative stress. In the present report, we demonstrate that nuclear transcription factors Nrf2 and Nrf1 associate with Jun (c-Jun, Jun-B and Jun-D) proteins to upregulate ARE-mediated expression and coordinated induction of detoxifying enzymes in response to antioxidants and xenobiotics. Nrf-Jun association/heterodimerization and binding to the ARE required unknown cytosolic factor(s). Nrf2 containing one mutated leucine in its leucine zipper region was more efficient in upregulation of ARE-mediated gene expression, as compared to Nrf1 with two mutated leucines.
抗氧化反应元件（ARE）介导的基因表达以及编码解毒酶的基因的协同诱导是细胞抵御氧化应激的一种至关重要的机制。在本报告中，我们证明核转录因子Nrf2和Nrf1与Jun（c-Jun、Jun-B和Jun-D）蛋白结合，以响应抗氧化剂和外源性物质上调ARE介导的基因表达以及解毒酶的协同诱导。Nrf-Jun结合/异二聚化以及与ARE的结合需要未知的胞质因子。与含有两个突变亮氨酸的Nrf1相比，在其亮氨酸拉链区域含有一个突变亮氨酸的Nrf2在上调ARE介导的基因表达方面更有效。
