Imperial College London
Alternate

Emeritus ProfessorMurraySelkirk

Faculty of Natural Sciences, Department of Life Sciences

Emeritus Professor in Molecular Parasitology
 
 
 
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Contact

 

+44 (0)20 7594 5214m.selkirk Website

 
 
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Location

 

204Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{White:2016:10.1371/journal.ppat.1005977,
author = {White, RR and Ponsford, AH and Weekes, MP and Rodrigues, RB and Ascher, DB and Mol, M and Selkirk, ME and Gygi, SP and Sanderson, CM and Artavanis-Tsakonas, K},
doi = {10.1371/journal.ppat.1005977},
journal = {PLoS Pathogens},
title = {Ubiquitin-Dependent Modification of Skeletal Muscle by the Parasitic Nematode, Trichinella spiralis},
url = {http://dx.doi.org/10.1371/journal.ppat.1005977},
volume = {12},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Trichinella spiralis is a muscle-specific parasitic worm that is uniquely intracellular. T. spiralisreprograms terminally differentiated skeletal muscle cells causing them to de-differentiateand re-enter the cell cycle, a process that cannot occur naturally in mammalian skeletalmuscle cells, but one that holds great therapeutic potential. Although the host ubiquitin pathwayis a common target for viruses and bacteria during infection, its role in parasite pathogenesishas 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 toTsUBE2L3, a novel and conserved T. spiralis enzyme located in the secretory organ of theparasite during the muscle stages of infection. TsUBE2L3 cannot function with any T.spiralissecreted E3, but specifically binds to a panel of human RING E3 ligases, including the RBRE3 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 downregulationin protein ubiquitination, most predominantly affecting motor, sarcomeric and extracellularmatrix proteins, thus mediating their stabilization with regards to proteasomal degradation.This effect is not observed in the presence of the mammalian ortholog, suggesting functionaldivergence in the evolution of the parasite protein. These findings demonstrate the firstexample of host-parasite interactions via a parasite-derived Ub conjugating enzyme; an E2that demonstrates a novel muscle protein stabilization function.
AU  - White,RR
AU  - Ponsford,AH
AU  - Weekes,MP
AU  - Rodrigues,RB
AU  - Ascher,DB
AU  - Mol,M
AU  - Selkirk,ME
AU  - Gygi,SP
AU  - Sanderson,CM
AU  - Artavanis-Tsakonas,K
DO  - 10.1371/journal.ppat.1005977
PY  - 2016///
SN  - 1553-7366
TI  - Ubiquitin-Dependent Modification of Skeletal Muscle by the Parasitic Nematode, Trichinella spiralis
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1005977
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000392193200017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/49684
VL  - 12
ER  -
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