Hippo unleashed! Proteome-scale analysis reveals new views of Hippo pathway biology

In animals, Hippo pathways control cell proliferation and morphogenesis, regulate tissue architecture, and restrain tumorigenesis. A recent surge in interest has linked these pathways to cell junction proteins and cell polarity proteins, as well as the microtubule cytoskeleton. Three large-scale protein interaction studies, including one by Couzens et al. in this week's issue, have dramatically increased the scope of information about Hippo pathways. In addition to adding nuance to mechanistic interactions that were already known or suspected, these works implicate membrane trafficking, activity of the phosphatase PP6, and cytokinetic regulation in Hippo signaling. A mechanism of pathway inhibition involving the endosomal-lysosomal axis emerges, and dramatic remodeling of protein interactions upon phosphatase inhibition is revealed. Overall, these studies provide a rich new resource for the expanded study of this highly conserved pathway.