2018
DOI: 10.1038/s41467-018-04757-w
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Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner

Abstract: Phosphorylation-dependent YAP translocation is a well-known intracellular mechanism of the Hippo pathway; however, the molecular effectors governing YAP cytoplasmic translocation remains undefined. Recent findings indicate that oncogenic YAP paradoxically suppresses Wnt activity. Here, we show that Wnt scaffolding protein Dishevelled (DVL) is responsible for cytosolic translocation of phosphorylated YAP. Mutational inactivation of the nuclear export signal embedded in DVL leads to nuclear YAP retention, with a… Show more

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Cited by 62 publications
(55 citation statements)
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References 68 publications
(133 reference statements)
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“…YAP can be phosphorylated by VP, and phosphorylated YAP binds to proteins and remains in the cytoplasm [28,29]. Therefore, the destruction of YAP/TAZ nuclear transport by VP can inhibit the EMT process to a certain extent [30], a nding that was also con rmed in this study.…”
Section: Discussionsupporting
confidence: 81%
“…YAP can be phosphorylated by VP, and phosphorylated YAP binds to proteins and remains in the cytoplasm [28,29]. Therefore, the destruction of YAP/TAZ nuclear transport by VP can inhibit the EMT process to a certain extent [30], a nding that was also con rmed in this study.…”
Section: Discussionsupporting
confidence: 81%
“…Some evidence suggests potential cooperativity between these proteins in the context of tumorigenesis. Dvl physically interacts with phosphorylated YAP, promoting YAP nuclear export, and suppressing its transcriptional activity, while treatment with Wnt1 or Wnt3a induces YAP dephosphorylation, reducing its binding to Dvl and thus promoting its nuclear translocation (Lee et al, 2018). Given that Wnt5a also induces YAP dephosphorylation (Park et al, 2015), Wnt5a might also activate YAP by abrogating its binding to Dvl, thus promoting YAP nuclear translocation.…”
Section: Future Directions and Conclusionmentioning
confidence: 99%
“…In Drosophila Yki nuclear export has been shown to also depend on other factors. For example, Yki can interact directly with the Wnt‐related protein Dishevelled (Dvl), which has a NES (Lee et al, ).…”
Section: Overview Of the Hippo‐yap Signaling Pathwaymentioning
confidence: 99%