title: Time-dependent hierarchical regulation analysis: deciphering cellular adaptation.
abstract: Cells adapt to changes in their environment by the concerted action of many different regulatory mechanisms. Examples of such mechanisms are feedback inhibition by intermediates of metabolism, covalent modification of enzymes and changes in the abundance of mRNAs and proteins. These mechanisms act in parallel at different levels in the cellular hierarchy while regulating a single process. Existing hierarchical regulation analysis determines the relative importance of these mechanisms when the cell regulates a transition from one steady-state to another. Here, the analysis is extended to the regulation of time-dependent phenomena, for which two methods are introduced and illustrated with a kinetic model incorporating transcription and translation of metabolic enzymes.
authors.affiliation: BioCentre Amsterdam, Faculty of Earth and Life Sciences, Department of Molecular Cell Physiology, Vrije Universiteit, De Boelelaan 1085, NL-1081 HV, Amsterdam, The Netherlands. frank.bruggeman@falw.vu.nl
authors.forename: F J
authors.initials: FJ
authors.lastname: Bruggeman
authors.forename: J
authors.initials: J
authors.lastname: de Haan
authors.forename: H
authors.initials: H
authors.lastname: Hardin
authors.forename: J
authors.initials: J
authors.lastname: Bouwman
authors.forename: S
authors.initials: S
authors.lastname: Rossell
authors.forename: K
authors.initials: K
authors.lastname: van Eunen
authors.forename: B M
authors.initials: BM
authors.lastname: Bakker
authors.forename: H V
authors.initials: HV
authors.lastname: Westerhoff
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000465:Algorithms; D000818:Animals; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D005246:Feedback / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D020543:Proteome / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020543:Proteome; D012333:RNA, Messenger