Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling
- Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling
- Jung, H; Kim, BG; Han, WH; Lee, JH; Cho, JY; Park, WS; Maurice, MM; Han, JK; Lee, MJ; Finley, D; Jho, EH
- Date Issued
- 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 b-catenin, which suggests an oncogenic role for Usp14 via enhancement of Wnt/beta-catenin signaling.
- Article Type
- ONCOGENESIS, vol. 2013, no. 2, page. E64 - E64, 2013-08
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