title: Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling.
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.
authors: Department of Life Science, The University of Seoul, Seoul, Korea.
authors: H
authors: H
authors: Jung
authors: B-G
authors: BG
authors: Kim
authors: W H
authors: WH
authors: Han
authors: J H
authors: JH
authors: Lee
authors: J-Y
authors: JY
authors: Cho
authors: W S
authors: WS
authors: Park
authors: M M
authors: MM
authors: Maurice
authors: J-K
authors: JK
authors: Han
authors: M J
authors: MJ
authors: Lee
authors: D
authors: D
authors: Finley
authors: E-H
authors: EH
authors: Jho
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