Deubiquitination of dishevelled by usp14 is required for wnt signaling

H. Jung; B. G. Kim; W. H. Han; J. H. Lee; J. Y. Cho; W. S. Park; M. M. Maurice; J. K. Han; M. J. Lee; D. Finley; E. H. Jho

doi:10.1038/oncsis.2013.28

Deubiquitination of dishevelled by usp14 is required for wnt signaling

H. Jung, B. G. Kim, W. H. Han, J. H. Lee, J. Y. Cho, W. S. Park, M. M. Maurice, J. K. Han, M. J. Lee, D. Finley, E. H. Jho

Department of Life Science

Research output: Contribution to journal › Article › peer-review

92 Scopus citations

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.

Original language	English
Article number	e64
Journal	Oncogenesis
Volume	2
DOIs	https://doi.org/10.1038/oncsis.2013.28
State	Published - 2013

Keywords

Usp14
Wnt
deubiquitinase
dishevelled
ubiquitination

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/oncsis.2013.28

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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.",

keywords = "Usp14, Wnt, deubiquitinase, dishevelled, ubiquitination",

author = "H. Jung and Kim, {B. G.} and Han, {W. H.} and Lee, {J. H.} and Cho, {J. Y.} and Park, {W. S.} and Maurice, {M. M.} and Han, {J. K.} and Lee, {M. J.} and D. Finley and Jho, {E. H.}",

year = "2013",

doi = "10.1038/oncsis.2013.28",

language = "English",

volume = "2",

journal = "Oncogenesis",

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T1 - Deubiquitination of dishevelled by usp14 is required for wnt signaling

AU - Jung, H.

AU - Kim, B. G.

AU - Han, W. H.

AU - Lee, J. H.

AU - Cho, J. Y.

AU - Park, W. S.

AU - Maurice, M. M.

AU - Han, J. K.

AU - Lee, M. J.

AU - Finley, D.

AU - Jho, E. H.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Usp14

KW - Wnt

KW - deubiquitinase

KW - dishevelled

KW - ubiquitination

UR - http://www.scopus.com/inward/record.url?scp=84883185607&partnerID=8YFLogxK

U2 - 10.1038/oncsis.2013.28

DO - 10.1038/oncsis.2013.28

M3 - Article

AN - SCOPUS:84883185607

SN - 2157-9024

VL - 2

JO - Oncogenesis

JF - Oncogenesis

M1 - e64

ER -

Deubiquitination of dishevelled by usp14 is required for wnt signaling

Abstract

Keywords

UN SDGs

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