ArticlePLoS pathogens2016
Ubiquitin-Dependent Modification of Skeletal Muscle by the Parasitic Nematode, Trichinella spiralis.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 40 citations in OpenAlex.
- Development and verification of a novel risk model related to ubiquitination linked with prognosis and therapeutic response in clear cell renal cell carcinoma.Scientific reports · 2024Article
- Echinococcus granulosus ubiquitin-conjugating enzymes (E2D2 and E2N) promote the formation of liver fibrosis in TGFβ1-induced LX-2 cells.Parasites & vectors · 2024Article
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- Quantitative label-free proteomic analysis of excretory-secretory proteins in different developmental stages of Trichinella spiralis.Veterinary research · 2024Article
- Pyruvate dehydrogenase B regulates myogenic differentiation via the FoxP1-Arih2 axis.Journal of cachexia, sarcopenia and muscle · 2023Article
- Large-scale proteomic analysis ofFrontiers in parasitology · 2023Article
- Using Graph-Based Signatures to Guide Rational Antibody Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations.Protein science : a publication of the Protein Society · 2021Article
- mCSM-membrane: predicting the effects of mutations on transmembrane proteins.Nucleic acids research · 2020Article
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- Arih2 gene influences immune response and tissue development in chicken.Bioscience reports · 2019Article
- Accumulation of α-2,6-sialyoglycoproteins in the Muscle Sarcoplasm Due toOpen life sciences · 2019Article
- DynaMut: predicting the impact of mutations on protein conformation, flexibility and stability.Nucleic acids research · 2018Article
- Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam.Nature genetics · 2018Article
- SDM: a server for predicting effects of mutations on protein stability.Nucleic acids research · 2017Article
- mCSM-NA: predicting the effects of mutations on protein-nucleic acids interactions.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Trichinella spiralis is a muscle-specific parasitic worm that is uniquely intracellular. T. spiralis reprograms terminally differentiated skeletal muscle cells causing them to de-differentiate and re-enter the cell cycle, a process that cannot occur naturally in mammalian skeletal muscle cells, but one that holds great therapeutic potential. Although the host ubiquitin pathway is a common target for viruses and bacteria during infection, its role in parasite pathogenesis has been largely overlooked. Here we demonstrate that the secreted proteins of T. spiralis contain E2 Ub-conjugating and E3 Ub-ligase activity. The E2 activity is attributed to TsUBE2L3, a novel and conserved T. spiralis enzyme located in the secretory organ of the parasite during the muscle stages of infection. TsUBE2L3 cannot function with any T.spiralis secreted E3, but specifically binds to a panel of human RING E3 ligases, including the RBR E3 ARIH2 with which it interacts with a higher affinity than the mammalian ortholog UbcH7/UBE2L3. Expression of TsUBE2L3 in skeletal muscle cells causes a global downregulation in protein ubiquitination, most predominantly affecting motor, sarcomeric and extracellular matrix proteins, thus mediating their stabilization with regards to proteasomal degradation. This effect is not observed in the presence of the mammalian ortholog, suggesting functional divergence in the evolution of the parasite protein. These findings demonstrate the first example of host-parasite interactions via a parasite-derived Ub conjugating enzyme; an E2 that demonstrates a novel muscle protein stabilization function.
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