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.
authors: Division of Life Sciences, Korea University, Seoul, Korea.
authors: M R
authors: MR
authors: Byun
authors: Division of Life Sciences, Korea University, Seoul, Korea.
authors: J-H
authors: JH
authors: Hwang
authors: Division of Life Sciences, Korea University, Seoul, Korea.
authors: A R
authors: AR
authors: Kim
authors: Division of Life Sciences, Korea University, Seoul, Korea.
authors: K M
authors: KM
authors: Kim
authors: College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul, Korea.
authors: E S
authors: ES
authors: Hwang
authors: Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors: M B
authors: MB
authors: Yaffe
authors: Division of Life Sciences, Korea University, Seoul, Korea.
authors: J-H
authors: JH
authors: Hong
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics; D000217:Acyltransferases; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D000090683:Hippo Signaling Pathway; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D014157:Transcription Factors; D060509:Wnt3A Protein; D000217:Acyltransferases; C486363:tafazzin protein, mouse; D017346:Protein Serine-Threonine Kinases