Dysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the trichoydsplasia spinulosa polyomavirus

Journal of the European Academy of Dermatology and Venereology : JEADV
J H WuS K Tyring

Abstract

Trichodysplasia spinulosa (TS) is a disfiguring folliculocentric cutaneous disease caused by infection with the trichodysplasia spinulosa polyomavirus (TSPyV). The TSPyV genome contains splice variants encoding the middle tumour (mT) antigen, although the potential role for TSPyV mT antigen in disease development remains unknown. The current study was designed to investigate the mechanistic properties of TSPyV mT antigen, which may further our understanding of TS pathogenesis and provide insight into potential therapies. A lentiviral packaging system was used to create an inducible cell line expressing TSPyV mT antigen. Proteins were extracted, separated by SDS-PAGE and subjected to Western blot analysis. Co-immunoprecipitation experiments and mutational analyses were also performed to evaluate protein-protein interactions of mT antigen. We describe a novel mechanism of action for mT antigen that involves hyperactivation of MEK, ERK and MNK1. Our findings suggest that dysregulation of these key signalling molecules depends upon TSPyV mT antigen interaction with protein phosphatase 2A (PP2A) via intact Zn binding motifs. Given that PP2A interaction and MEK/ERK/MNK1 phosphorylation are associated with high levels of cell prolifer...Continue Reading

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Mar 15, 2015·Journal of the European Academy of Dermatology and Venereology : JEADV·J H WuS K Tyring
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Feb 26, 2016·Critical Reviews in Biochemistry and Molecular Biology·Nathan Wlodarchak, Yongna Xing

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Citations

Aug 5, 2020·Transplant Infectious Disease : an Official Journal of the Transplantation Society·Deepika NarayananStephen K Tyring
Mar 24, 2018·Frontiers in Microbiology·Els van der Meijden, Mariet Feltkamp
Aug 15, 2019·International Journal of Molecular Sciences·Ugo Moens, Andrew Macdonald

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