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

dc.contributor.authorWallach, Thomas
dc.contributor.authorSchellenberg, Katja
dc.contributor.authorMaier, Bert
dc.contributor.authorKalathur, Ravi Kiran Reddy
dc.contributor.authorPorras, Pablo
dc.contributor.authorWanker, Erich E.
dc.contributor.authorFutschik, Matthias E.
dc.contributor.authorKramer, Achim
dc.date.accessioned2018-12-07T14:53:43Z
dc.date.available2018-12-07T14:53:43Z
dc.date.issued2013-03
dc.description.abstractEssentially all biological processes depend on protein-protein interactions (PPIs). Timing of such interactions is crucial for regulatory function. Although circadian (similar to 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.
dc.description.sponsorshipBMBF [NGFN1/2]; EU; Helmholtz Association; Portuguese Fundacao para a Ciencia e a Tecnologia; RKRK [SFRH/BPD/70718/2010]; Deutsche Forschungsgemeinschaft [SFB740, SFB618]
dc.identifier.doi10.1371/journal.pgen.1003398
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/10400.1/11654
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library Science
dc.relationSYSTEMS BIOLOGY APPROACH TO UNRAVEL THE MOLECULAR MECHANISMS INVOLVED IN T-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA
dc.relationEuropean Consortium on Synaptic Protein Networks in Neurological and Psychiatric Diseases
dc.subjectGene-Expression
dc.subjectClock Protein
dc.subjectTranscription
dc.subjectStability
dc.subjectPhosphorylation
dc.subjectIdentification
dc.subjectOscillation
dc.subjectMechanism
dc.subjectBiology
dc.subjectCells
dc.titleDynamic circadian protein-protein interaction networks predict temporal organization of cellular functions
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSYSTEMS BIOLOGY APPROACH TO UNRAVEL THE MOLECULAR MECHANISMS INVOLVED IN T-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA
oaire.awardTitleEuropean Consortium on Synaptic Protein Networks in Neurological and Psychiatric Diseases
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F70718%2F2010/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/241498/EU
oaire.citation.issue3
oaire.citation.startPagee1003398
oaire.citation.titlePlos Genetics
oaire.citation.volume9
oaire.fundingStreamFP7
person.familyNameKalathur
person.familyNameFutschik
person.givenNameRavi Kiran Reddy
person.givenNameMatthias
person.identifier.ciencia-idA71B-AD01-3501
person.identifier.orcid0000-0003-2894-3345
person.identifier.orcid0000-0002-6245-8071
person.identifier.scopus-author-id22940879800
person.identifier.scopus-author-id14017989400
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication029974a3-d5b1-48f5-a44c-ca866e556336
relation.isAuthorOfPublicationd58f3269-c7e1-4c22-b094-5cfe6750821b
relation.isAuthorOfPublication.latestForDiscoveryd58f3269-c7e1-4c22-b094-5cfe6750821b
relation.isProjectOfPublication55e70560-7c4e-40bf-8fc7-eb7a93214c3d
relation.isProjectOfPublicationfac926af-b2a4-44a7-95b3-662fe7a1d868
relation.isProjectOfPublication.latestForDiscoveryfac926af-b2a4-44a7-95b3-662fe7a1d868

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