Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation

• Published in: Cell death and differentiation Vol. 21; no. 6; pp. 854 - 863
• Main Authors: Byun, M R, Hwang, J-H, Kim, A R, Kim, K M, Hwang, E S, Yaffe, M B, Hong, J-H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2014; Nature Publishing Group
• Subjects: 14-3-3 Proteins - genetics; 631/136/142; 631/80/86; 692/698/690/796; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cancer research; Cell Biology; Cell Cycle Analysis; Cell death; Cell Differentiation - genetics; Cell growth; Cell Proliferation - genetics; Gene Expression Regulation, Developmental; Humans; Kinases; Life Sciences; Lipoproteins; Localization; Medical research; Mice; NIH 3T3 Cells; Original Paper; Osteoblasts - metabolism; Osteogenesis - genetics; Protein-Serine-Threonine Kinases - genetics; Proteins; Signal Transduction - genetics; Stem Cells; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Wnt3A Protein - genetics; Wnt3A Protein - metabolism; United States > US; Massachusetts; Hippo pathway; osteoblast; TAZ; Wnt; PP1A
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2014.8

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 β , 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.