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

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.

SUBMITTER: Wallach T

PROVIDER: S-EPMC3610820 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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

Wallach Thomas T Schellenberg Katja K Maier Bert B Kalathur Ravi Kiran Reddy RK Porras Pablo P Wanker Erich E EE Futschik Matthias E ME Kramer Achim A

PLoS genetics 20130328 3

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 ...[more]

PMID: 23555304

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

Publications

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

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