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Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions

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Item Type:Article
Title:Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions
Creators Name:Wallach, T and Schellenberg, K and Maier, B and Kalathur, R.K. and Porras, P. and Wanker, E.E. and Futschik, M.E. and Kramer, A.
Abstract:Essentially all biological processes depend on protein-protein interactions (PPIs). Timing of such interactions is crucial for regulatory function. Although circadian (~24-hour) clocks constitute fundamental cellular timing mechanisms regulating important physiological processes, PPI dynamics on this timescale are largely unknown. Here, we identified 109 novel PPIs among circadian clock proteins via a yeast-two-hybrid approach. Among them, the interaction of protein phosphatase 1 and CLOCK/BMAL1 was found to result in BMAL1 destabilization. We constructed a dynamic circadian PPI network predicting the PPI timing using circadian expression data. Systematic circadian phenotyping (RNAi and overexpression) suggests a crucial role for components involved in dynamic interactions. Systems analysis of a global dynamic network in liver revealed that interacting proteins are expressed at similar times likely to restrict regulatory interactions to specific phases. Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc.) contributing to temporal organization of cellular physiology in an unprecedented manner.
Keywords:ARNTL Transcription Factors, Cell Cycle, Circadian Clocks, Circadian Rhythm, CLOCK Proteins, Epidermal Growth Factor Receptor, HEK293 Cells, Protein Interaction Maps, Protein Phosphatase 1, Signal Transduction
Source:PLoS Genetics
Publisher:Public Library of Science
Page Range:e1003398
Date:March 2013
Official Publication:https://doi.org/10.1371/journal.pgen.1003398
PubMed:View item in PubMed

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