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Author (up) Wallach, T.; Schellenberg, K.; Maier, B.; Kalathur, R.K.R.; Porras, P.; Wanker, E.E.; Futschik, M.E.; Kramer, A. url  doi
  Title Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions Type Journal Article
  Year 2013 Publication PLoS Genetics Abbreviated Journal PLoS Genet  
  Volume 9 Issue 3 Pages e1003398  
  Keywords ARNTL Transcription Factors/genetics/metabolism; *CLOCK Proteins/genetics/metabolism; Cell Cycle/genetics/physiology; Circadian Clocks/*genetics; Circadian Rhythm/*genetics; HEK293 Cells; Humans; Protein Interaction Maps/*genetics; Protein Phosphatase 1/genetics/metabolism; Receptor, Epidermal Growth Factor/metabolism; Signal Transduction  
  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.  
  Address Laboratory of Chronobiology, Charite-Universitatsmedizin, Berlin, Germany  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1553-7390 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23555304 Approved no  
  Call Number refbase @ admin @ Serial 35130  
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