Ding Chenbo, Fan Xiaobo, Wu Guoqiu
Medical School of Southeast University, Nanjing, China.
Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
J Cell Mol Med. 2017 Jan;21(1):193-202. doi: 10.1111/jcmm.12955. Epub 2016 Sep 21.
Peroxiredoxins (PRDXs), a ubiquitous family of redox-regulating proteins, are reported of potential to eliminate various reactive oxygen species (ROS). As a major member of the antioxidant enzymes, PRDX1 can become easily over-oxidized on its catalytically active cysteine induced by a variety of stimuli in vitro and in vivo. In nucleus, oligomeric PRDX1 directly associates with p53 or transcription factors such as c-Myc, NF-κB and AR, and thus affects their bioactivities upon gene regulation, which in turn induces or suppresses cell death. Additionally, PRDX1 in cytoplasm has anti-apoptotic potential through direct or indirect interactions with several ROS-dependent (redox regulation) effectors, including ASK1, p66 , GSTpi/JNK and c-Abl kinase. PRDX1 is proven to be a versatile molecule regulating cell growth, differentiation and apoptosis. Recent studies have found that PRDX1 and/or PRDX1-regulated ROS-dependent signalling pathways play an important role in the progression and metastasis of human tumours, particularly in breast, oesophageal and lung cancers. In this paper, we review the structure, effector functions of PRDX1, its role in cancer and the pivotal role of ROS in anticancer treatment.
过氧化物酶(PRDXs)是一类广泛存在的氧化还原调节蛋白家族,据报道具有清除各种活性氧(ROS)的潜力。作为抗氧化酶的主要成员,PRDX1在体内外受到各种刺激时,其催化活性半胱氨酸很容易被过度氧化。在细胞核中,寡聚体PRDX1直接与p53或转录因子如c-Myc、NF-κB和AR结合,从而在基因调控中影响它们的生物活性,进而诱导或抑制细胞死亡。此外,细胞质中的PRDX1通过与几种ROS依赖性(氧化还原调节)效应器直接或间接相互作用,包括ASK1、p66、GSTpi/JNK和c-Abl激酶,具有抗凋亡潜力。PRDX1被证明是一种调节细胞生长、分化和凋亡的多功能分子。最近的研究发现,PRDX1和/或PRDX1调节的ROS依赖性信号通路在人类肿瘤的进展和转移中起重要作用,特别是在乳腺癌、食管癌和肺癌中。在本文中,我们综述了PRDX1的结构、效应器功能、其在癌症中的作用以及ROS在抗癌治疗中的关键作用。