Journal
JOURNAL OF CELL SCIENCE
Volume 133, Issue 2, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.230425
Keywords
Hippo pathway; TEAD transcription factors; YAP/TAZ; Mechanotransduction
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Funding
- Associazione Italiana per la Ricerca sul Cancro (AIRC) foundation investigator grant [21392]
- Cassa di Risparmio di Padova e Rovigo (CARIPARO) foundation grant Eccellenza [2017]
- University of Padova Budget, Integrato per la Ricerca dei Dipartimenti (BIRD) grant
- AIRC postdoctoral fellowship
- Fondazione Umberto Veronesi postoctoral fellowship
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YAP and TAZ proteins are transcriptional coactivators encoded by paralogous genes, which shuttle between the cytoplasm and the nucleus in response to multiple inputs, including the Hippo pathway. In the nucleus, they pair with DNA-binding factors of the TEAD family to regulate gene expression. Nuclear YAP/TAZ promote cell proliferation, organ overgrowth, survival to stress and dedifferentiation of post-mitotic cells into their respective tissue progenitors. YAP/TAZ are required for growth of embryonic tissues, wound healing and organ regeneration, where they are activated by cell-intrinsic and extrinsic cues. Surprisingly, this activity is dispensable in many adult self-renewing tissues, where YAP/TAZ are constantly kept in check. YAP/TAZ lay at the center of a complex regulatory network including cell-autonomous factors but also cell- and tissue-level structural features such as the mechanical properties of the cell microenvironment, the establishment of cell-cell junctions and of basolateral tissue polarity. Enhanced levels and activity of YAP/TAZ are observed in many cancers, where they sustain tumor growth, drug resistance and malignancy. In this Cell Science at a Glance article and the accompanying poster, we review the biological functions of YAP/TAZ and their regulatory mechanisms, and highlight their position at the center of a complex signaling network.
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