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了解哺乳动物 AP 内切核酸酶(APE1)的不同功能,将其作为癌症治疗的有前途的工具。

Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment.

机构信息

Department of Biomedical Sciences and Technologies, University of Udine, Piazzale Kolbe 4, 33100, Udine, Italy.

出版信息

Cell Mol Life Sci. 2010 Nov;67(21):3589-608. doi: 10.1007/s00018-010-0486-4. Epub 2010 Aug 13.

Abstract

The apurinic endonuclease 1/redox factor-1 (APE1) has a crucial function in DNA repair and in redox signaling in mammals, and recent studies identify it as an excellent target for sensitizing tumor cells to chemotherapy. APE1 is an essential enzyme in the base excision repair pathway of DNA lesions caused by oxidation and alkylation. As importantly, APE1 also functions as a redox agent maintaining transcription factors involved in cancer promotion and progression in an active reduced state. Very recently, a new unsuspected function of APE1 in RNA metabolism was discovered, opening new perspectives for this multifunctional protein. These observations underline the necessity to understand the molecular mechanisms responsible for fine-tuning its different biological functions. This survey intends to give an overview of the multifunctional roles of APE1 and their regulation in the context of considering this protein a promising tool for anticancer therapy.

摘要

脱嘌呤/脱嘧啶核酸内切酶 1/氧化还原因子-1(APE1)在哺乳动物的 DNA 修复和氧化还原信号转导中具有重要功能,最近的研究将其确定为使肿瘤细胞对化疗敏感的理想靶点。APE1 是由氧化和烷基化引起的 DNA 损伤碱基切除修复途径中的必需酶。同样重要的是,APE1 还作为一种氧化还原调节剂,使涉及癌症促进和进展的转录因子保持在活性还原状态。最近,发现了 APE1 在 RNA 代谢中的一个新的意想不到的功能,为这个多功能蛋白开辟了新的视角。这些观察结果强调了有必要了解负责精细调节其不同生物学功能的分子机制。本综述旨在概述 APE1 的多功能作用及其在考虑该蛋白作为一种有前途的抗癌治疗工具的情况下的调节。

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