2020
Systems biology approaches to macromolecules: the role of dynamic protein assemblies in information processing
Rukhlenko O, Kholodenko B, Kolch W. Systems biology approaches to macromolecules: the role of dynamic protein assemblies in information processing. Current Opinion In Structural Biology 2020, 67: 61-68. PMID: 33126139, PMCID: PMC8062579, DOI: 10.1016/j.sbi.2020.09.007.Peer-Reviewed Original ResearchConceptsProtein assembliesProtein complex dynamicsDynamic protein assembliesMacromolecular protein assembliesSignal transduction networksSystems biology approachMEK-ERK pathwayProtein complexesTransduction networksCellular processesBiology approachMolecular machinesRAS-RAFOncogenic mutationsStructural studiesDrug resistanceTemporal dynamicsAssemblyRecent progressTumorigenesisMutationsPicture highlightsFine tuningPathwayDynamic processExtensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
Kennedy S, Jarboui M, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn M, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko B, Iglesias-Martinez L, Ryan C, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn D, Kolch W. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D. Nature Communications 2020, 11: 499. PMID: 31980649, PMCID: PMC6981206, DOI: 10.1038/s41467-019-14224-9.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptor (EGFR) networkGrowth factor receptor networkFundamental biological processesColorectal cancer cellsCancer cellsEGFR networkTranscriptional regulationProtein complexesExtensive rewiringCellular phenotypesInteraction networksBiological processesOncogenic mutationsOncogenic KRAS mutationsReceptor networkGenetic alterationsProtein expressionPPInsMutationsCellsInteractorsPhosphorylationRewiringPoor patient outcomesSignal flow
2019
Mapping connections in signaling networks with ambiguous modularity
Lill D, Rukhlenko O, Mc Elwee A, Kashdan E, Timmer J, Kholodenko B. Mapping connections in signaling networks with ambiguous modularity. Npj Systems Biology And Applications 2019, 5: 19. PMID: 31149348, PMCID: PMC6533310, DOI: 10.1038/s41540-019-0096-1.Peer-Reviewed Original ResearchConceptsModular Response AnalysisProtein abundanceProtein complexesNetwork reconstructionDownstream modulesRetroactive interactionsUpstream moduleComputational restorationNetwork modulesSuite of methodsAbundanceSuch complexesExperimental approachComplexesProteinEnzymePathwaySequestration effectNetwork responseDifferent modules
2005
Signaling through Receptors and Scaffolds: Independent Interactions Reduce Combinatorial Complexity
Borisov N, Markevich N, Hoek J, Kholodenko B. Signaling through Receptors and Scaffolds: Independent Interactions Reduce Combinatorial Complexity. Biophysical Journal 2005, 89: 951-966. PMID: 15923229, PMCID: PMC1366644, DOI: 10.1529/biophysj.105.060533.Peer-Reviewed Original ResearchConceptsProtein complexesComplex signaling networksDistinct physiological responsesSignaling networksAdaptor proteinDocking siteMolecular eventsTemporal dynamicsPhysiological responsesDistinct sitesIndependent interactionsBranched networkSeparate domainsMolecular speciesDomain-oriented approachCombinatorial increaseReceptorsIndividual sitesSitesComplexesScaffoldsSpeciesTens of thousandsProteinDifferent sites