Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

被引：116

作者：

Byun, M. R. ^{[1
]}

Hwang, J-H ^{[1
]}

Kim, A. R. ^{[1
]}

Kim, K. M. ^{[1
]}

Hwang, E. S. ^{[2
,3
]}

Yaffe, M. B. ^{[4
]}

Hong, J-H ^{[1
]}

机构：

[1] Korea Univ, Div Life Sci, Seoul, South Korea

[2] Ewha Womans Univ, Coll Pharm, Seoul, South Korea

[3] Ewha Womans Univ, Res Program Top5, Seoul, South Korea

[4] MIT, Dept Biol, Ctr Canc Res, Cambridge, MA 02139 USA

来源：

CELL DEATH AND DIFFERENTIATION | 2014年 / 21卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

TAZ; Wnt; Hippo pathway; PP1A; osteoblast; HIGH BONE MASS; EPITHELIAL-MESENCHYMAL TRANSITION; RECEPTOR-RELATED PROTEIN-5; LRP5 MISSENSE MUTATION; CELL SELF-RENEWAL; HIPPO PATHWAY; CARDIOMYOCYTE PROLIFERATION; TYROSINE PHOSPHORYLATION; HEART SIZE; CATENIN;

D O I：

10.1038/cdd.2014.8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 GSK3 beta, 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.

引用

页码：854 / 863

页数：10

共 47 条

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