YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response
Open accessAbstract
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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Wnt3a may not only activate canonical Wnt signaling but also crosstalk with other pathways, such as Hippo/YAP.
“This may be explained by that Wnt3a not only activates the canonical Wnt signaling but also crosstalks with other pathways, such as the Hippo/YAP pathway”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Azzolin et al., 2014
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- Authors
- Azzolin, L., Panciera, T., Soligo, S., Enzo, E., Bicciato, S., Dupont, S., Bresolin, S., Frasson, C., Basso, G., Guzzardo, V., Fassina, A., Cordenonsi, M., & Piccolo, S.
- Affiliations
- University of Padua (IT)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Cordenonsi, Michelangelo
- Piccolo, Stefano
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 158
- Issue
- 1
- Pages
- 157-170
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2027150010
- Cited by
- 1,094
- References
- 5
- Citations by year
- 2026: 61 · 2025: 71 · 2024: 83 · 2023: 83 · 2022: 99 · 2021: 87 · 2020: 122 · 2019: 101 · 2018: 120 · 2017: 88 · 2016: 90 · 2015: 68 · 2014: 18 · 2013: 1
- FWCI
- 43.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Padua Research Archive (University of Padova) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- YAP, TAZ, Hippo signaling pathway, Wnt signaling, β-catenin destruction complex, β-TrCP, crypt regeneration, embryonic stem cell self-renewal, organ size control, tumor suppression
- MeSH terms
- YAP-Signaling Proteins, Acyltransferases, Animals, Cell Line, Humans, Models, Biological, Phosphoproteins, Transcription Factors, Cell Cycle Proteins, Adaptor Proteins, Signal Transducing, Wnt Proteins, beta Catenin, Mice, Embryonic Stem Cells, HEK293 Cells
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