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; J. H. Hong

doi:10.1038/cdd.2014.8

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^*
, J. H. Hong

^*Corresponding author for this work

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

100 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 language	English
Pages (from-to)	854-863
Number of pages	10
Journal	Cell Death and Differentiation
Volume	21
Issue number	6
DOIs	https://doi.org/10.1038/cdd.2014.8
Publication status	Published - 2014 Jun

Bibliographical note

Funding Information:
Acknowledgements. This work was supported by Basic Science Research Programs (2011-0022926) of the National Research Foundation of Korea (NRF) and grants (A120349 and A120476) from the Korea Healthcare Technology R&D Project, Republic of Korea.

Keywords

Hippo pathway
PP1A
TAZ
Wnt
osteoblast

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1038/cdd.2014.8

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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, PP1A, TAZ, Wnt, osteoblast",

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 Hong, \{J. H.\}",

note = "Funding Information: Acknowledgements. This work was supported by Basic Science Research Programs (2011-0022926) of the National Research Foundation of Korea (NRF) and grants (A120349 and A120476) from the Korea Healthcare Technology R\&D Project, Republic of Korea.",

year = "2014",

month = jun,

doi = "10.1038/cdd.2014.8",

language = "English",

volume = "21",

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AU - Byun, M. R.

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AU - Kim, K. M.

AU - Hwang, E. S.

AU - Yaffe, M. B.

AU - Hong, J. H.

N1 - Funding Information: Acknowledgements. This work was supported by Basic Science Research Programs (2011-0022926) of the National Research Foundation of Korea (NRF) and grants (A120349 and A120476) from the Korea Healthcare Technology R&D Project, Republic of Korea.

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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.

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KW - osteoblast

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SN - 1350-9047

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JO - Cell Death and Differentiation

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ER -

Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

Abstract

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Keywords

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