Glorieux Christophe, Zamocky Marcel, Sandoval Juan Marcelo, Verrax Julien, Calderon Pedro Buc
Toxicology and Cancer Biology Research Group, Louvain Drug Research Institute, Université catholique de Louvain, 1200 Brussels, Belgium.
Division of Biochemistry, Department of Chemistry, University of Natural Resources and Life Sciences (BOKU), A-1190 Vienna, Austria; Institute of Molecular Biology, Slovak Academy of Sciences, SK-84551 Bratislava, Slovakia.
Free Radic Biol Med. 2015 Oct;87:84-97. doi: 10.1016/j.freeradbiomed.2015.06.017. Epub 2015 Jun 25.
Catalase is an important antioxidant enzyme that dismutates hydrogen peroxide into water and molecular oxygen. The catalase gene has all the characteristics of a housekeeping gene (no TATA box, no initiator element sequence, high GC content in promoter) and a core promoter that is highly conserved among species. We demonstrate in this review that within this core promoter, the presence of DNA binding sites for transcription factors, such as NF-Y and Sp1, plays an essential role in the positive regulation of catalase expression. Additional transcription factors, such as FoxO3a, are also involved in this regulatory process. There is strong evidence that the protein Akt/PKB in the PI3K signaling pathway plays a major role in the expression of catalase by modulating the activity of FoxO3a. Over the past decade, other transcription factors (PPARγ, Oct-1, etc.), as well as genetic, epigenetic, and posttranscriptional processes, have emerged as crucial contributors to the regulation of catalase expression. Altered expression levels of catalase have been reported in cancer tissues compared to their normal counterparts. Deciphering the molecular mechanisms that regulate catalase expression could, therefore, be of crucial importance for the future development of pro-oxidant cancer chemotherapy.
过氧化氢酶是一种重要的抗氧化酶,它能将过氧化氢歧化为水和分子氧。过氧化氢酶基因具有管家基因的所有特征(无TATA盒、无起始子元件序列、启动子中GC含量高)以及在物种间高度保守的核心启动子。我们在本综述中表明,在这个核心启动子内,转录因子如NF-Y和Sp1的DNA结合位点的存在,在过氧化氢酶表达的正调控中起着至关重要的作用。其他转录因子,如FoxO3a,也参与了这一调控过程。有强有力的证据表明,PI3K信号通路中的蛋白Akt/PKB通过调节FoxO3a的活性,在过氧化氢酶的表达中起主要作用。在过去十年中,其他转录因子(PPARγ、Oct-1等)以及遗传、表观遗传和转录后过程,已成为过氧化氢酶表达调控的关键因素。与正常组织相比,癌症组织中过氧化氢酶的表达水平已被报道发生改变。因此,破译调节过氧化氢酶表达的分子机制可能对促氧化癌症化疗的未来发展至关重要。