Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

M. R. Byun, J. H. Hwang, A. R. Kim, K. M. Kim, E. S. Hwang, M. B. Yaffe, Jeong-Ho Hong

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

TAZ, a transcriptional modulator, has a key role in cell proliferation, differentiation and stem cell self-renewal. TAZ activity is regulated by several signalling pathways, including Hippo, GPCR and Wnt signalling, but the regulatory mechanisms of TAZ activation are not yet clearly understood. In this report, we show that TAZ is regulated by canonical Wnt signalling during osteogenic differentiation. Wnt3a increases TAZ expression and an inhibitor of GSK3β, a downstream effector of Wnt signalling, induces TAZ. Wnt3a facilitates the dephosphorylation of TAZ, which stabilises TAZ and prevents it from binding 14-3-3 proteins, thus inducing the nuclear localisation of TAZ. Dephosphorylation of TAZ occurs via PP1A, and depletion of PP1A blocks Wnt3a-induced TAZ stabilisation. Wnt3a-induced TAZ activates osteoblastic differentiation and siRNA-induced TAZ depletion decreases Wnt3a-induced osteoblast differentiation. Taken together, these results show that TAZ mediates Wnt3a-stimulated osteogenic differentiation through PP1A, suggesting that the Wnt signal regulates the Hippo pathway.

Original languageEnglish
Pages (from-to)854-863
Number of pages10
JournalCell Death and Differentiation
Volume21
Issue number6
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

14-3-3 Proteins
Osteoblasts
Small Interfering RNA
Cell Differentiation
Carrier Proteins
Cell Proliferation
Cell Self Renewal

Keywords

  • Hippo pathway
  • osteoblast
  • PP1A
  • TAZ
  • Wnt

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation. / Byun, M. R.; Hwang, J. H.; Kim, A. R.; Kim, K. M.; Hwang, E. S.; Yaffe, M. B.; Hong, Jeong-Ho.

In: Cell Death and Differentiation, Vol. 21, No. 6, 01.01.2014, p. 854-863.

Research output: Contribution to journalArticle

Byun, M. R. ; Hwang, J. H. ; Kim, A. R. ; Kim, K. M. ; Hwang, E. S. ; Yaffe, M. B. ; Hong, Jeong-Ho. / Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation. In: Cell Death and Differentiation. 2014 ; Vol. 21, No. 6. pp. 854-863.
@article{b22e46a005794b1b9647ce53de7563fc,
title = "Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation",
abstract = "TAZ, a transcriptional modulator, has a key role in cell proliferation, differentiation and stem cell self-renewal. TAZ activity is regulated by several signalling pathways, including Hippo, GPCR and Wnt signalling, but the regulatory mechanisms of TAZ activation are not yet clearly understood. In this report, we show that TAZ is regulated by canonical Wnt signalling during osteogenic differentiation. Wnt3a increases TAZ expression and an inhibitor of GSK3β, a downstream effector of Wnt signalling, induces TAZ. Wnt3a facilitates the dephosphorylation of TAZ, which stabilises TAZ and prevents it from binding 14-3-3 proteins, thus inducing the nuclear localisation of TAZ. Dephosphorylation of TAZ occurs via PP1A, and depletion of PP1A blocks Wnt3a-induced TAZ stabilisation. Wnt3a-induced TAZ activates osteoblastic differentiation and siRNA-induced TAZ depletion decreases Wnt3a-induced osteoblast differentiation. Taken together, these results show that TAZ mediates Wnt3a-stimulated osteogenic differentiation through PP1A, suggesting that the Wnt signal regulates the Hippo pathway.",
keywords = "Hippo pathway, osteoblast, PP1A, TAZ, Wnt",
author = "Byun, {M. R.} and Hwang, {J. H.} and Kim, {A. R.} and Kim, {K. M.} and Hwang, {E. S.} and Yaffe, {M. B.} and Jeong-Ho Hong",
year = "2014",
month = "1",
day = "1",
doi = "10.1038/cdd.2014.8",
language = "English",
volume = "21",
pages = "854--863",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

AU - Byun, M. R.

AU - Hwang, J. H.

AU - Kim, A. R.

AU - Kim, K. M.

AU - Hwang, E. S.

AU - Yaffe, M. B.

AU - Hong, Jeong-Ho

PY - 2014/1/1

Y1 - 2014/1/1

N2 - TAZ, a transcriptional modulator, has a key role in cell proliferation, differentiation and stem cell self-renewal. TAZ activity is regulated by several signalling pathways, including Hippo, GPCR and Wnt signalling, but the regulatory mechanisms of TAZ activation are not yet clearly understood. In this report, we show that TAZ is regulated by canonical Wnt signalling during osteogenic differentiation. Wnt3a increases TAZ expression and an inhibitor of GSK3β, a downstream effector of Wnt signalling, induces TAZ. Wnt3a facilitates the dephosphorylation of TAZ, which stabilises TAZ and prevents it from binding 14-3-3 proteins, thus inducing the nuclear localisation of TAZ. Dephosphorylation of TAZ occurs via PP1A, and depletion of PP1A blocks Wnt3a-induced TAZ stabilisation. Wnt3a-induced TAZ activates osteoblastic differentiation and siRNA-induced TAZ depletion decreases Wnt3a-induced osteoblast differentiation. Taken together, these results show that TAZ mediates Wnt3a-stimulated osteogenic differentiation through PP1A, suggesting that the Wnt signal regulates the Hippo pathway.

AB - TAZ, a transcriptional modulator, has a key role in cell proliferation, differentiation and stem cell self-renewal. TAZ activity is regulated by several signalling pathways, including Hippo, GPCR and Wnt signalling, but the regulatory mechanisms of TAZ activation are not yet clearly understood. In this report, we show that TAZ is regulated by canonical Wnt signalling during osteogenic differentiation. Wnt3a increases TAZ expression and an inhibitor of GSK3β, a downstream effector of Wnt signalling, induces TAZ. Wnt3a facilitates the dephosphorylation of TAZ, which stabilises TAZ and prevents it from binding 14-3-3 proteins, thus inducing the nuclear localisation of TAZ. Dephosphorylation of TAZ occurs via PP1A, and depletion of PP1A blocks Wnt3a-induced TAZ stabilisation. Wnt3a-induced TAZ activates osteoblastic differentiation and siRNA-induced TAZ depletion decreases Wnt3a-induced osteoblast differentiation. Taken together, these results show that TAZ mediates Wnt3a-stimulated osteogenic differentiation through PP1A, suggesting that the Wnt signal regulates the Hippo pathway.

KW - Hippo pathway

KW - osteoblast

KW - PP1A

KW - TAZ

KW - Wnt

UR - http://www.scopus.com/inward/record.url?scp=84899951327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899951327&partnerID=8YFLogxK

U2 - 10.1038/cdd.2014.8

DO - 10.1038/cdd.2014.8

M3 - Article

VL - 21

SP - 854

EP - 863

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 6

ER -