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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. pp. 1-7.

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Abstract

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 :
NameEmailORCID
Maluquer de Motes, Carlosc.maluquerdemotes@surrey.ac.ukUNSPECIFIED
Smith, Geoffrey LUNSPECIFIEDUNSPECIFIED
Date : 2017
Identification Number : 10.1099/jgv.0.000946
Copyright Disclaimer : 000946 © 2017 The Authors This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/, 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 : 09 Oct 2017 13:04
URI: http://epubs.surrey.ac.uk/id/eprint/842488

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