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      YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response.

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          Abstract

          The Hippo transducers YAP/TAZ have been shown to play positive, as well as negative, roles in Wnt signaling, but the underlying mechanisms remain unclear. Here, we provide biochemical, functional, and genetic evidence that YAP and TAZ are integral components of the β-catenin destruction complex that serves as cytoplasmic sink for YAP/TAZ. In Wnt-ON cells, YAP/TAZ are physically dislodged from the destruction complex, allowing their nuclear accumulation and activation of Wnt/YAP/TAZ-dependent biological effects. YAP/TAZ are required for intestinal crypt overgrowth induced by APC deficiency and for crypt regeneration ex vivo. In Wnt-OFF cells, YAP/TAZ are essential for β-TrCP recruitment to the complex and β-catenin inactivation. In Wnt-ON cells, release of YAP/TAZ from the complex is instrumental for Wnt/β-catenin signaling. In line, the β-catenin-dependent maintenance of ES cells in an undifferentiated state is sustained by loss of YAP/TAZ. This work reveals an unprecedented signaling framework relevant for organ size control, regeneration, and tumor suppression.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          1097-4172
          0092-8674
          Jul 03 2014
          : 158
          : 1
          Affiliations
          [1 ] Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
          [2 ] Center for Genome Research, Department of Biomedical Sciences, University of Modena and Reggio Emilia, via Giuseppe Campi 287, 41100 Modena, Italy.
          [3 ] Clinical and Experimental Hematology, Department of Paediatrics, University of Padua, via Giustiniani 3, 35128 Padua, Italy.
          [4 ] Department of Medicine, University of Padua School of Medicine, via Gabelli 61, 35126 Padua, Italy.
          [5 ] Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy. Electronic address: michelangelo.cordenonsi@unipd.it.
          [6 ] Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy. Electronic address: piccolo@bio.unipd.it.
          Article
          S0092-8674(14)00734-X
          10.1016/j.cell.2014.06.013
          24976009
          73c5229f-722c-4ad4-8fb5-432e073840ec
          Copyright © 2014 Elsevier Inc. All rights reserved.
          History

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