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

Research output: Contribution to journalArticle

60 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 Jun

Keywords

  • Hippo pathway
  • PP1A
  • TAZ
  • Wnt
  • osteoblast

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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