UMMS Affiliation

Program in Molecular Medicine

Publication Date


Document Type



Biochemistry | Cell Biology | Enzymes and Coenzymes | Molecular Biology | Translational Medical Research


The Hippo (Hpo) tumor suppressor pathway is an evolutionarily conserved signaling pathway that controls tissue growth and organ size in species ranging from Drosophila to human, and its malfunction has been implicated in many types of human cancer. In this study, we conducted a kinome screen and identified Happyhour (Hppy)/MAP4K3 as a novel player in the Hpo pathway. Our biochemical study showed that Hppy binds and phosphorylates Wts. Our genetic experiments suggest that Hppy acts in parallel and partial redundantly with Misshapen (Msn)/MAP4K4 to regulate Yki nuclear localization and Hpo target gene expression in Drosophila wing imaginal discs. Furthermore, we showed that cytoskeleton stress restricts Yki nuclear localization through Hppy and Msn when Hpo activity is compromised, thus providing an explanation for the Wts-dependent but Hpo-independent regulation of Yki in certain contexts. Our study has unraveled an additional layer of complexity in the Hpo signaling pathway and laid down a foundation for exploring how different upstream regulators feed into the core Hpo pathway.


Hippo, ISC, MAP4K, Wts, Yki, organ size, UMCCTS funding

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DOI of Published Version



Cell Discov. 2015 Nov 24;1:15038. doi: 10.1038/celldisc.2015.38. eCollection 2015. Link to article on publisher's site

Journal/Book/Conference Title

Cell discovery

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.