Evans A R, Limp-Foster M, Kelley M R
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Mutat Res. 2000 Oct 16;461(2):83-108. doi: 10.1016/s0921-8777(00)00046-x.
The DNA base excision repair (BER) pathway is responsible for the repair of cellular alkylation and oxidative DNA damage. A crucial and the second step in the BER pathway involves the cleavage of baseless sites in DNA by an AP endonuclease. The major AP endonuclease in mammalian cells is Ape1/ref-1. Ape1/ref-1 is a multifunctional protein that is not only responsible for repair of AP sites, but also functions as a reduction-oxidation (redox) factor maintaining transcription factors in an active reduced state. Ape1/ref-1 has been shown to stimulate the DNA binding activity of numerous transcription factors that are involved in cancer promotion and progression such as Fos, Jun, NF(B, PAX, HIF-1(, HLF and p53. Ape1/ref-1 has also been implicated in the activation of bioreductive drugs which require reduction in order to be active and has been shown to interact with a subunit of the Ku antigen to act as a negative regulator of the parathyroid hormone promoter, as well as part of the HREBP transcription factor complex. Ape1/ref-1 levels have been found to be elevated in a number of cancers such as ovarian, cervical, prostate, rhabdomyosarcomas and germ cell tumors and correlated with the radiosensitivity of cervical cancers. In this review, we have attempted to try and assimilated as much data concerning Ape1/ref-1 and incorporate the rapidly growing information on Ape1/ref-1 in a wide variety of functions and systems.
DNA碱基切除修复（BER）途径负责修复细胞中的烷基化和氧化性DNA损伤。BER途径中的关键步骤及第二步涉及由AP核酸内切酶切割DNA中的无碱基位点。哺乳动物细胞中的主要AP核酸内切酶是Ape1/ref-1。Ape1/ref-1是一种多功能蛋白，不仅负责修复AP位点，还作为一种还原氧化（redox）因子，使转录因子维持在活性还原状态。已证明Ape1/ref-1可刺激众多参与癌症促进和进展的转录因子的DNA结合活性，如Fos、Jun、NF(B、PAX、HIF-1(、HLF和p53。Ape1/ref-1还与生物还原药物的激活有关，这些药物需要还原才能发挥活性，并且已证明它与Ku抗原的一个亚基相互作用，作为甲状旁腺激素启动子的负调节因子，以及HREBP转录因子复合物的一部分。已发现Ape1/ref-1水平在多种癌症中升高，如卵巢癌、宫颈癌、前列腺癌、横纹肌肉瘤和生殖细胞肿瘤，并且与宫颈癌的放射敏感性相关。在本综述中，我们试图收集尽可能多的关于Ape1/ref-1的数据，并将关于Ape1/ref-1在各种功能和系统中迅速增长的信息整合进来。
