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Vaccinia virus protein A49 activates Wnt signalling by targeting the E3 ligase b-TrCP

Maluquer de Motes, Carlos and Smith, Geoffrey L (2017) Vaccinia virus protein A49 activates Wnt signalling by targeting the E3 ligase b-TrCP Journal of General Virology, 98. pp. 3086-3092.

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Vaccinia virus (VACV) encodes multiple proteins inhibiting the NF-kB signalling pathway. One of these, A49, targets the E3 ubiquitin ligase b-TrCP, which is responsible for the ubiquitylation and consequential proteosomal degradation of IkBa and the release of the NF-kB heterodimer. b-TrCP is a pleiotropic enzyme ubiquitylating multiple cellular substrates, including the transcriptional activator b-catenin. Here we demonstrate that A49 can activate the Wnt signalling pathway, a critical pathway that is involved in cell cycle and cell differentiation, and is controlled by b-catenin. The data presented show that the expression of A49 ectopically or during VACV infection causes accumulation of b-catenin, and that A49 triggering of Wnt signalling is dependent on binding b-TrCP. This is consistent with A49 blocking the ability of b-TrCP to recognize b-catenin and IkBa, and possibly other cellular targets. Thus, A49 targeting of b-TrCP affects multiple cellular pathways, including the NF-kB and Wnt signalling cascades.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Maluquer de Motes,
Smith, Geoffrey L
Date : 17 October 2017
DOI : 10.1099/jgv.0.000946
Copyright Disclaimer : © 2017 The Authors. Published by the Microbiology Society. This is an open access article under the terms of the, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords : vaccinia virus; protein A49; b-transducin repeat containing protein; Wnt pathway; b-catenin
Depositing User : Jane Hindle
Date Deposited : 09 Oct 2017 13:04
Last Modified : 16 Jan 2019 18:57

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