Program in Molecular Medicine
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
Li, Shuangxi; Cho, Yong Suk; Yue, Tao; Ip, Y. Tony; and Jiang, Jin, "Overlapping functions of the MAP4K family kinases Hppy and Msn in Hippo signaling" (2015). UMass Center for Clinical and Translational Science Supported Publications. 181.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.