Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling

Collection with item attached
2013
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/477064.do
DOI
10.1038/oncsis.2013.28
Title
Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling
Description
We thank Kay Hofmann (University of Cologne) for his assistance withbioinformatics. This work was supported by funding from the NationalResearch Foundation of Korea (2010-0021106 and 2012R1A2A2A01012472 toE-h.J. and 2012-0003217 to M.J.L.) and by the National Institutes ofHealth grant GM095526 (DF). HJ was supported by the Brain Korea 21program.
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 b-catenin, which suggests an oncogenic role for Usp14 via enhancement of Wnt/beta-catenin signaling.
provenance
Made available in Cube on 2018-09-28T11:56:26Z (GMT). No. of bitstreams: 0
language
English
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
orcid
Lee, Min Jae/0000-0002-3252-6467; Maurice, Madelon/0000-0001-6885-5361
accessioned
2018-09-28T11:56:26Z
available
2018-09-28T11:56:26Z
issued
2013
citation
ONCOGENESIS(2)
issn
2157-9024
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/477064.do
Funder
교육과학기술부
Funding Program
일반연구자지원
Project ID
1345174049
Jurisdiction
Rep.of Korea
Project Name
Functional analysis of novel regulators of Wnt signal transduction
rights
openAccess
subject
Wnt
dishevelled
deubiquitinase
Usp14
ubiquitination
type
article


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