Hippo Pathway Phylogenetics Predicts Monoubiquitylation of Salvador and Merlin/Nf2

摘要: Abstract Recently we employed phylogenetics to predict that the cellular interpretation of TGF-b signals is modulated bymonoubiquitylation cycles affecting Smad4 signal transducer/tumor suppressor. This prediction was subsequentlyvalidated by experiments in flies, frogs and mammalian cells. Here apply a phylogenetic approach Hippo pathwayand two its transducers, Salvador Merlin/Nf2 (also tumor suppressor) are regulated bymonoubiquitylation. regulatory mechanism does not lead protein degradation but instead serves as highlyefficient ‘‘off/on’’ switch when subsequently deubiquitylated. Overall, our study shows creativeapplication can new roles for pathway components mechanisms regulatingintercellular signaling pathways. Citation: Wisotzkey RG, Konikoff CE, Newfeld SJ (2012) Pathway Phylogenetics Predicts Monoubiquitylation Merlin/Nf2. PLoS ONE 7(12):e51599. doi:10.1371/journal.pone.0051599Editor: Jitesh Pratap, Rush University Medical Center, United States AmericaReceived August 5, 2012; Accepted November 8, Published December 14, 2012Copyright: 2012 et al. an open-access article distributed under terms Creative Commons Attribution License, which permitsunrestricted use, distribution, reproduction any medium, provided original author source credited.Funding: CEK supported part National Science Foundation DBI-0939454. SJN Institutes Health HG002516. The fundershad no role design, data collection analysis, decision publish, or preparation manuscript.Competing Interests: authors have declared competing interests exist.* E-mail: newfeld@asu.edu. These contributed equally this work.