APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1.
APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1.
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DOI：
10.2174/1874467211205010036
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发表时间：
2012-01
影响因子：
2.7
通讯作者：
Fishel ML
中科院分区：
文献类型：
--
作者：
Kelley MR;Georgiadis MM;Fishel ML
大多数癌症的异质性降低了许多癌症杀伤方案的治疗效果。因此，最有希望的治疗方法是阻断癌症生存所必需的多种信号通路。在这方面最有前途的蛋白质之一是APE 1，其还原-氧化活性影响多种癌症存活机制，包括生长、增殖、转移、血管生成和应激反应。随着单独使用APE 1氧化还原特异性抑制剂或与开发APE 1 DNA修复抑制剂结合的持续研究，现在有可能进一步描述APE 1氧化还原，修复和蛋白质-蛋白质相互作用的作用。以前，使用siRNA或过表达方法，虽然有价值，但并没有给出APE 1的两个主要功能的清晰图像，因为这两种技术都严重改变了细胞环境。此外，使用氧化还原特异性APE 1抑制剂APX 3330，现在可以研究抑制APE 1的氧化还原信号传导如何影响多种肿瘤途径，并可以增强现有癌症治疗方案的有效性。由于APE 1是VEGF以及与血管生成和肿瘤微环境相关的其他分子的上游效应子，因此它也被研究为年龄相关性黄斑变性和糖尿病视网膜病变的可能治疗方法。本文综述了APE 1的所有功能，同时重点介绍了其氧化还原活性。它还讨论了APE 1在许多癌症中的表达改变以及选择性抑制氧化还原调节的治疗潜力，这是密集的临床前研究的主题。
The heterogeneity of most cancers diminishes the treatment effectiveness of many cancer-killing regimens. Thus, treatments that hold the most promise are ones that block multiple signaling pathways essential to cancer survival. One of the most promising proteins in that regard is APE1, whose reduction-oxidation activity influences multiple cancer survival mechanisms, including growth, proliferation, metastasis, angiogenesis, and stress responses. With the continued research using APE1 redox specific inhibitors alone or coupled with developing APE1 DNA repair inhibitors it will now be possible to further delineate the role of APE1 redox, repair and protein-protein interactions. Previously, use of siRNA or over expression approaches, while valuable, do not give a clear picture of the two major functions of APE1 since both techniques severely alter the cellular milieu. Additionally, use of the redox-specific APE1 inhibitor, APX3330, now makes it possible to study how inhibition of APE1’s redox signaling can affect multiple tumor pathways and can potentiate the effectiveness of existing cancer regimens. Because APE1 is an upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for age-related macular degeneration and diabetic retinopathy. This paper reviews all of APE1’s functions, while heavily focusing on its redox activities. It also discusses APE1’s altered expression in many cancers and the therapeutic potential of selective inhibition of redox regulation, which is the subject of intense preclinical studies.