Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling

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Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling

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Title: Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling
Author: Jung, H; Kim, B-G; Han, W H; Lee, J H; Cho, J-Y; Park, W S; Maurice, M M; Han, J-K; Lee, M J; Finley, D; Jho, E-h

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Citation: Jung, H., B. Kim, W. H. Han, J. H. Lee, J. Cho, W. S. Park, M. M. Maurice, et al. 2013. “Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling.” Oncogenesis 2 (8): e64. doi:10.1038/oncsis.2013.28. http://dx.doi.org/10.1038/oncsis.2013.28.
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Abstract: Dishevelled (Dvl) is a key regulator of Wnt signaling both in the canonical and non-canonical pathways. Here we report the identification of a regulatory domain of ubiquitination (RDU) in the C-terminus of Dvl. Mutations in the RDU resulted in accumulation of polyubiquitinated forms of Dvl, which were mainly K63 linked. Small interfering RNA-based screening identified Usp14 as a mediator of Dvl deubiquitination. Genetic and chemical suppression of Usp14 activity caused an increase in Dvl polyubiquitination and significantly impaired downstream Wnt signaling. These data suggest that Usp14 functions as a positive regulator of the Wnt signaling pathway. Consistently, tissue microarray analysis of colon cancer revealed a strong correlation between the levels of Usp14 and β-catenin, which suggests an oncogenic role for Usp14 via enhancement of Wnt/β-catenin signaling.
Published Version: doi:10.1038/oncsis.2013.28
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759127/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11877122
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