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首页> 外文期刊>Molecular and Cellular Biology >Genetic Evidence that Small Maf Proteins Are Essential for the Activation of Antioxidant Response Element-Dependent Genes
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Genetic Evidence that Small Maf Proteins Are Essential for the Activation of Antioxidant Response Element-Dependent Genes

机译：小黑手党蛋白是激活抗氧化反应元件相关基因必不可少的遗传证据。

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While small Maf proteins have been suggested to be essential for the Nrf2-mediated activation of antioxidant response element (ARE)-dependent genes, the extent of their requirement remains to be fully documented. To address this issue, we generated mafG::mafF double-mutant mice possessing MafK as the single available small Maf. Induction of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene was significantly impaired in double-mutant mice treated with butylated hydroxyanisole, while other ARE-dependent genes were less affected. Similarly, in a keap1-null background, where many of the ARE-dependent genes are constitutively activated in an Nrf2-dependent manner, only a subset of ARE-dependent genes, including NQO1, were sensitive to a simultaneous deficiency in MafG and MafF. Examination of single and double small maf mutant cells revealed that MafK also contributes to the induction of ARE-dependent genes. To obtain decisive evidence, we established mafG::mafK::mafF triple-mutant fibroblasts that completely lack small Mafs and turned out to be highly susceptible to oxidative stress. We found that induction in response to diethyl maleate was abolished in a wider range of ARE-dependent genes in the triple-mutant cells. These data explicitly demonstrate that small Mafs play critical roles in the inducible expression of a significant portion of ARE-dependent genes.
机译：虽然已经提出了小的Maf蛋白对于Nrf2介导的抗氧化反应元件（ARE）依赖性基因的激活至关重要，但其需求程度仍有待充分证明。为了解决这个问题，我们生成了具有MafK作为单个可用小Maf的 mafG :: mafF 双突变小鼠。在用丁基化羟基茴香醚处理的双突变小鼠中，NAD（P）H：醌氧化还原酶1（ NQO1 ）基因的诱导显着受损，而其他ARE依赖性基因受到的影响较小。同样，在 keap1 -null背景下，许多ARE依赖性基因以Nrf2依赖性方式被组成性激活，只有一部分ARE依赖性基因，包括 NQO1 ，对同时出现MafG和MafF缺乏症敏感。检查单个和两个小的 maf 突变细胞表明，MafK还有助于诱导ARE依赖性基因。为了获得决定性证据，我们建立了 mafG :: mafK :: mafF 三突变成纤维细胞，该细胞完全缺乏小Mafs，并且具有高度的Mafs。容易受到氧化应激。我们发现三联突变细胞中更广泛的ARE依赖性基因中消除了对马来酸二乙酯的诱导诱导。这些数据明确表明，小黑手党在ARE依赖基因的重要部分的可诱导表达中起关键作用。

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