How many transcription factors does it take to turn on the heme oxygenase-1 gene?
How many transcription factors does it take to turn on the heme oxygenase-1 gene?
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DOI：
10.1165/rcmb.2006-0340tr
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发表时间：
2007-02-01
影响因子：
6.4
通讯作者：
Cook, Julia L.
中科院分区：
文献类型：
--
作者：
Alam, Jawed;Cook, Julia L.
与环境沟通并对环境中的变化做出反应的能力，特别是那些不利性质的变化，对细胞功能和生存至关重要。整体细胞应激反应的一个关键组成部分包括基因表达程序的调整，有利于表现出能够挫败并最终消除应激条件分子成分的蛋白质。提供这种细胞保护活性的一种蛋白质是血红素加氧酶-1（HO-1），其是一种催化血红素催化剂中的限速反应的酶（即，b-型血红素分子的氧化裂解产生等摩尔量的胆绿素IX α、一氧化碳和铁）。由于反应产物具有有效的抗氧化、抗炎和信号传导特性，HO-1基因（hmox 1）在各种细胞应激条件下经常被激活。细胞使用多种信号通路和转录因子来微调它们对特定环境的反应。在这些因子中，热休克因子、核因子-κ B、核因子-红细胞2和激活蛋白-1家族的成员可以说是脊椎动物细胞应激反应的最重要的调节因子。虽然在各个家族之间存在功能重叠，但每个家族广泛地调节细胞应激反应的不同方面，因此，除了一些例外，调节不同靶基因组的表达。据我们所知，hmox 1是独特的，因为它被认为是直接调节所有这些压力响应转录因子。在这篇文章中，我们提供了一个审查和分析的数据支持这一主张。
The ability to communicate with the environment and respond to changes-particularly those of an adverse nature-within that environment is critical for cell function and survival. A key component of the overall cellular stress response includes adjustments in the gene expression program in favor of proteins that manifest activities capable of frustrating and eventually eliminating the molecular constituents of the stress condition. One protein providing such cytoprotective activity is heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting reaction in heme catabolism (i.e., the oxidative cleavage of b-type heme molecules to yield equimolar quantities of biliverdin IX alpha, carbon monoxide, and iron). Because of the potent antioxidant, anti-inflammatory, and signaling properties of the reaction products, the HO-1 gene (hmox1) is frequently activated under a variety of cellular stress conditions. Cells use multiple signaling pathways and transcription factors to fine-tune their response to a specific circumstance. Among these factors, members of the heat-shock factor, nuclear factor-kappa B, nuclear factor-erythroid 2, and activator protein-1 families are arguably the most important regulators of the cellular stress response in vertebrates. Although there is functional overlap between individual families, each broadly regulates different aspects of the cellular stress response and thus, with some exceptions, modulates the expression of different sets of targets genes. To the best of our knowledge, hmox1 is unique in that it is proposed to be directly regulated by all four of these stress-responsive transcription factors. In this article we provide a review and analysis of the data supporting this proposition.