Hippo pathway phylogenetics predicts monoubiquitylation of Salvador and Merlin/Nf2.

ABSTRACT: Recently we employed phylogenetics to predict that the cellular interpretation of TGF-β signals is modulated by monoubiquitylation cycles affecting the Smad4 signal transducer/tumor suppressor. This prediction was subsequently validated by experiments in flies, frogs and mammalian cells. Here we apply a phylogenetic approach to the Hippo pathway and predict that two of its signal transducers, Salvador and Merlin/Nf2 (also a tumor suppressor) are regulated by monoubiquitylation. This regulatory mechanism does not lead to protein degradation but instead serves as a highly efficient "off/on" switch when the protein is subsequently deubiquitylated. Overall, our study shows that the creative application of phylogenetics can predict new roles for pathway components and new mechanisms for regulat

SUBMITTER: Wisotzkey RG 

PROVIDER: S-EPMC3522738 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature