title: Identification and characterisation of Emp53, the homologue of human tumor suppressor p53, from Echinococcus multilocularis: its role in apoptosis and the oxidative stress response.
abstract: 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.
authors: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors: Zhe
authors: Z
authors: Cheng
authors: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors: Shan
authors: S
authors: Zhu
authors: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors: Liang
authors: L
authors: Wang
authors: Medical College, Xiamen University, Xiamen, Fujian, China.
authors: Fan
authors: F
authors: Liu
authors: Medical College, Xiamen University, Xiamen, Fujian, China.
authors: Huimin
authors: H
authors: Tian
authors: Faculty of Medical Technology, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors: Theerakamol
authors: T
authors: Pengsakul
authors: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Parasitology Research Laboratory, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. Electronic address: wangyh@xmu.edu.cn.
authors: Yanhai
authors: Y
authors: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D004443:Echinococcosis / Q000469:parasitology*; D048210:Echinococcus multilocularis / Q000737:chemistry / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D015801:Helminth Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Apoptosis; DNA damage; Echinococcus multilocularis; Oxidative stress; p53