title: Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation.
abstract: Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle.
authors.affiliation: Centre for Cell Imaging, Institute of Integrative Biology, Liverpool, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Ankers
authors.affiliation: Centre for Cell Imaging, Institute of Integrative Biology, Liverpool, United Kingdom.|Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Raheela
authors.initials: R
authors.lastname: Awais
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Jones
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Boyd
authors.affiliation: Centre for Cell Imaging, Institute of Integrative Biology, Liverpool, United Kingdom.|Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Sheila
authors.initials: S
authors.lastname: Ryan
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Antony D
authors.initials: AD
authors.lastname: Adamson
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Claire V
authors.initials: CV
authors.lastname: Harper
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.|Department of Mathematics, University of Swansea, Swansea, United Kingdom.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Bridge
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: David G
authors.initials: DG
authors.lastname: Spiller
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Dean A
authors.identifier: 0000-0002-1570-5287
authors.initials: DA
authors.lastname: Jackson
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Pawel
authors.initials: P
authors.lastname: Paszek
authors.affiliation: Centre for Cell Imaging, Institute of Integrative Biology, Liverpool, United Kingdom.
authors.forename: Violaine
authors.initials: V
authors.lastname: Sée
authors.affiliation: Systems Microscopy Centre, Faculty of Life Sciences, Manchester, United Kingdom.
authors.forename: Michael Rh
authors.identifier: 0000-0002-3617-3232
authors.initials: MR
authors.lastname: White
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D050704:E2F4 Transcription Factor / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D016328:NF-kappa B
keywords: E2F; NF-kappaB; cell biology; cell cycle; computational biology; coupled systems; human; live cell imaging; mathematical modelling; systems biology