Identification and characterisation of Emp53, the homologue of human tumor suppressor p53, from Echinococcus multilocularis: its role in apoptosis and the oxidative stress response
Identification and characterisation of Emp53, the homologue of human tumor suppressor p53, from Echinococcus multilocularis: its role in apoptosis and the oxidative stress response
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多房棘球绦虫中人肿瘤抑制因子 p53 的同源物 Emp53 的鉴定和表征：其在细胞凋亡和氧化应激反应中的作用。
DOI：
10.1016/j.ijpara.2015.02.010
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发表时间：
2015-07-01
影响因子：
4
通讯作者：
Wang, Yanhai
中科院分区：
文献类型：
--
作者：
Cheng, Zhe;Zhu, Shan;Wang, Yanhai
狐狸绦虫的幼虫，多房棘球绦虫，引起泡状棘球蚴病，这被认为是人类最致命的蠕虫感染。由于它在宿主器官中发育，寄生虫必须进化出一种应激防御系统，以科普可能导致DNA损伤和基因组不稳定的各种遗传毒性和细胞应激。肿瘤抑制因子p53被称为“基因组的守护者”，在应对多种类型的应激和损伤中起着至关重要的作用。在本研究中，我们描述了从E.多房的，并证明它是哺乳动物肿瘤抑制基因p53的结构和功能同源物。我们发现Emp53特异性结合到含有常规p53结合位点的寡核苷酸上，表明它具有作为DNA结合转录因子的功能。抑制Emp53功能可以抑制紫外线诱导的E.多房后囊蚴，表明Emp53在DNA损伤后诱导细胞凋亡中的重要作用。我们还发现Emp53在抗氧化应激和调节氧化应激诱导的细胞凋亡中起重要作用。我们的研究结果表明，类似于它的人类对应物，Emp53在大肠杆菌DNA损伤反应和凋亡网络中起着核心作用。多房的这些结果可能有助于探索寄生蠕虫的应激防御机制，并可能为开发新的干预措施和治疗药物控制泡状棘球蚴病提供有用的信息。(C)2015年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
Larvae of the fox tapeworm, Echinococcus multilocularis, cause alveolar echinococcosis, which is considered to be the most lethal helminthic infection in humans. Since it develops in host organs, the parasite must have evolved a stress defense system to cope with various genotoxic and cellular stresses that may cause DNA damage and genomic instability. Tumor suppressor p53, well known as the "guardian of the genome", plays a vital role in response to many types of stress and damage. In the present study, we describe the characterisation of Emp53 from E. multilocularis and demonstrate that it is a structural and functional homologue of mammalian tumor suppressor p53. We show that Emp53 binds specifically to oligonucleotides containing conventional p53 binding sites, indicating that it exhibits a function as a DNA binding transcription factor. Inhibition of Emp53 function can suppress UV irradiation-induced apoptosis in the E. multilocularis metacestode, indicating an important role of Emp53 in the induction of apoptosis following DNA damage. We also reveal that Emp53 plays important roles in resistance to oxidative stress and regulation of oxidative stress-induced apoptosis. Our results suggest that, similar to its human counterpart, Emp53 plays a central role in the network of DNA damage responses and apoptosis in E. multilocularis. These results may help in exploring stress defense mechanisms of parasitic helminths and may provide useful information for the development of new interventions and therapeutic drugs for the control of alveolar echinococcosis. (C) 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.