METHODS: Experimentally defined transcription factor binding sites in the human thioredoxin and thioredoxin reductase gene promoters together with promoters of the major thioredoxin system substrates involved in regulating cellular redox status are discussed. An in silico approach was used to identify potential putative binding sites for these transcription factors in all of these promoters.
CONCLUSIONS: Our analysis reveals that many redox gene promoters contain the same transcription factor binding sites. Several of these transcription factors are in turn redox regulated. The ARE is present in several of these promoters and is bound by Nrf2 during various oxidative stress stimuli to upregulate gene expression. Other transcription factors also bind to these promoters during the same oxidative stress stimuli, with this redundancy supporting the importance of the antioxidant response. Putative transcription factor sites were identified in silico, which in combination with specific regulatory knowledge for that gene promoter may inform future experiments.
CONCLUSIONS: Redox proteins are involved in many cellular signalling pathways and aberrant expression can lead to disease or other pathological conditions. Therefore understanding how their expression is regulated is relevant for developing therapeutic agents that target these pathways.
方法:讨论了人类硫氧还蛋白和硫氧还蛋白还原酶基因启动子中实验定义的转录因子结合位点以及参与调节细胞氧化还原状态的主要硫氧还蛋白系统底物的启动子。使用计算机模拟方法来鉴定所有这些启动子中这些转录因子的潜在推定结合位点。
结论:我们的分析表明许多氧化还原基因启动子含有相同的转录因子结合位点。这些转录因子中的几个依次是氧化还原调节的。ARE存在于这些启动子中的几个中,并且在各种氧化应激刺激期间被Nrf2结合以上调基因表达。在相同的氧化应激刺激过程中,其他转录因子也与这些启动子结合,这种冗余支持了抗氧化反应的重要性。推定的转录因子位点在计算机中鉴定,结合该基因启动子的特定调控知识,可以为未来的实验提供信息。
结论:氧化还原蛋白参与许多细胞信号通路,异常表达可导致疾病或其他病理状况。因此,理解它们的表达如何被调节对于开发靶向这些途径的治疗剂是相关的。