Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling.
Oncogenesis
; 2: e64, 2013 Aug 19.
Article
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| MEDLINE
| ID: mdl-23958854
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 ß-catenin, which suggests an oncogenic role for Usp14 via enhancement of Wnt/ß-catenin signaling.
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MEDLINE
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En
Revista:
Oncogenesis
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2013
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Article