Vaccinia virus protein A49 activates Wnt signalling by targetting the E3 ligase β-TrCP.
The Journal of general virology
Society for General Microbiology
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Maluquer de Motes, C., & Smith, G. (2017). Vaccinia virus protein A49 activates Wnt signalling by targetting the E3 ligase β-TrCP.. The Journal of general virology, 98 (12), 3086-3092. https://doi.org/10.1099/jgv.0.000946
Vaccinia virus (VACV) encodes multiple proteins inhibiting the NF-κB signalling pathway. One of these, A49, targets the E3 ubiquitin ligase β-TrCP that is responsible for the ubiquitylation and consequential proteosomal degradation of IκBα and the release of the NF-κB heterodimer. β-TrCP is a pleiotropic enzyme ubiquitylating multiple cellular substrates including the transcriptional activator β-catenin. Here we demonstrate that A49 can activate the Wnt signalling pathway, a critical pathway involved in cell cycle and cell differentiation that is controlled by β-catenin. Data presented show that expression of A49 ectopically or during VACV infection causes accumulation of β-catenin, and that A49 triggering of Wnt signalling is dependent on binding β-TrCP. This is consistent with A49 blocking the ability of β-TrCP to recognise β-catenin and IκBα and possibly other cellular targets. Thus, A49 targetting of β-TrCP affects multiple cellular pathways, including the NF-κB and Wnt signalling cascades.
Wellcome Trust (090315/B/09/Z)
Embargo Lift Date
External DOI: https://doi.org/10.1099/jgv.0.000946
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276115
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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