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Identification and characterisation of Emp53, the homologue of human tumor suppressor p53, from Echinococcus multilocularis: its role in apoptosis and the oxidative stress response.
- Source :
-
International journal for parasitology [Int J Parasitol] 2015 Jul; Vol. 45 (8), pp. 517-26. Date of Electronic Publication: 2015 Apr 06. - Publication Year :
- 2015
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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.<br /> (Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Echinococcus multilocularis chemistry
Echinococcus multilocularis genetics
Helminth Proteins chemistry
Helminth Proteins genetics
Humans
Molecular Sequence Data
Multigene Family
Protein Structure, Tertiary
Sequence Alignment
Tumor Suppressor Protein p53 chemistry
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Apoptosis
Echinococcosis parasitology
Echinococcus multilocularis cytology
Echinococcus multilocularis metabolism
Helminth Proteins metabolism
Oxidative Stress
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0135
- Volume :
- 45
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- International journal for parasitology
- Publication Type :
- Academic Journal
- Accession number :
- 25858091
- Full Text :
- https://doi.org/10.1016/j.ijpara.2015.02.010