Hippo Pathway Phylogenetics Predicts Monoubiquitylation of Salvador and Merlin/Nf2

Robert G. Wisotzkey, Charlotte E. Konikoff, Stuart Newfeld

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 regulating intercellular signaling pathways.

Original languageEnglish (US)
Article numbere51599
JournalPloS one
Issue number12
StatePublished - Dec 14 2012

ASJC Scopus subject areas

  • General


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