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

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 thi...

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Main Authors: Thomas Wallach, Katja Schellenberg, Bert Maier, Ravi Kiran Reddy Kalathur, Pablo Porras, Erich E Wanker, Matthias E Futschik, Achim Kramer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-03-01
Series:PLoS Genetics
Online Access:http://europepmc.org/articles/PMC3610820?pdf=render
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author Thomas Wallach
Katja Schellenberg
Bert Maier
Ravi Kiran Reddy Kalathur
Pablo Porras
Erich E Wanker
Matthias E Futschik
Achim Kramer
author_facet Thomas Wallach
Katja Schellenberg
Bert Maier
Ravi Kiran Reddy Kalathur
Pablo Porras
Erich E Wanker
Matthias E Futschik
Achim Kramer
author_sort Thomas Wallach
collection DOAJ
description 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.
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spelling doaj.art-269b5e0039ae40f5896b6665e1412f932022-12-21T23:57:37ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-03-0193e100339810.1371/journal.pgen.1003398Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.Thomas WallachKatja SchellenbergBert MaierRavi Kiran Reddy KalathurPablo PorrasErich E WankerMatthias E FutschikAchim KramerEssentially 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.http://europepmc.org/articles/PMC3610820?pdf=render
spellingShingle Thomas Wallach
Katja Schellenberg
Bert Maier
Ravi Kiran Reddy Kalathur
Pablo Porras
Erich E Wanker
Matthias E Futschik
Achim Kramer
Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.
PLoS Genetics
title Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.
title_full Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.
title_fullStr Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.
title_full_unstemmed Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.
title_short Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.
title_sort dynamic circadian protein protein interaction networks predict temporal organization of cellular functions
url http://europepmc.org/articles/PMC3610820?pdf=render
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