RESUMEN

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 GSK3ß, 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.

Asunto(s)

Osteogénesis/genética , Transducción de Señal/genética , Factores de Transcripción/genética , Proteína Wnt3A/metabolismo , Proteínas 14-3-3/genética , Aciltransferasas , Animales , Diferenciación Celular/genética , Proliferación Celular/genética , Regulación del Desarrollo de la Expresión Génica , Vía de Señalización Hippo , Humanos , Ratones , Células 3T3 NIH , Osteoblastos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Factores de Transcripción/metabolismo , Proteína Wnt3A/genética