The Hippo Signaling Pathway Interactome

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Science  08 Nov 2013:
Vol. 342, Issue 6159, pp. 737-740
DOI: 10.1126/science.1243971

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Dissecting Hippo Interactions

The Hippo signaling pathway plays key roles in many processes, from cell proliferation and cell death to regulation of stem cells and cancer cells. Kwon et al. (p. 737, published 10 October) attempted to systematically identify all components of the pathway. A protein-protein interaction screen identified more than 200 interactions among approximately 150 proteins. A protein identified in the screen, Leash, restrained the activity of the transcriptional coactivator Yorkie, which regulates gene expression in response to Hippo signaling.


The Hippo pathway controls metazoan organ growth by regulating cell proliferation and apoptosis. Many components have been identified, but our knowledge of the composition and structure of this pathway is still incomplete. Using existing pathway components as baits, we generated by mass spectrometry a high-confidence Drosophila Hippo protein-protein interaction network (Hippo-PPIN) consisting of 153 proteins and 204 interactions. Depletion of 67% of the proteins by RNA interference regulated the transcriptional coactivator Yorkie (Yki) either positively or negatively. We selected for further characterization a new member of the alpha-arrestin family, Leash, and show that it promotes degradation of Yki through the lysosomal pathway. Given the importance of the Hippo pathway in tumor development, the Hippo-PPIN will contribute to our understanding of this network in both normal growth and cancer.

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