The Hippo pathway plays a key role in controlling organ growth and size. In mammals, core pathway components include the Lats1/2 and Mst1/2 kinases, which phosphorylate the transcriptional regulators, Taz and Yap. To identify novel upstream pathway regulators high throughput protein-protein interaction screens, called LUMIER (LUminescence-based Mammalian IntERactome) were performed together with a functional screen using a luciferase reporter that examines Hippo pathway responses. The screens revealed 1103 protein-protein interactions and 227 transcriptional regulators, which were particularly enriched in cytoskeletal regulators. A subset of these hits including BTK, Dvl1, Dvl2, Dvl3, Ing2, Magi2, Mark4 and Trip6 were validated by manual LUMIER assays and co-immunoprecipitation (Co-IP). Of particular interest was the microtubule dynamics regulatory protein MARK4. Loss of Mark4 prevents Taz activity demonstrating its role as a potential negative regulator of the Hippo pathway. Further studies could help decipher mechanisms of how Mark4 and the other cytoskeletal hits act to modulate the Hippo pathway.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/35681 |
| Date | 17 July 2013 |
| Creators | Shiban, Ahmed |
| Contributors | Attisano, Liliana |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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