title: Coordinated Pulses of mRNA and of Protein Translation or Degradation Produce EGF-Induced Protein Bursts.
abstract: Protein responses to extracellular cues are governed by gene transcription, mRNA degradation and translation, and protein degradation. In order to understand how these time-dependent processes cooperate to generate dynamic responses, we analyzed the response of human mammary cells to the epidermal growth factor (EGF). Integrating time-dependent transcript and protein data into a mathematical model, we inferred for several proteins their pre-and post-stimulus translation and degradation coefficients and found that they exhibit complex, time-dependent variation. Specifically, we identified strategies of protein production and degradation acting in concert to generate rapid, transient protein bursts in response to EGF. Remarkably, for some proteins, for which the response necessitates rapidly decreased abundance, cells exhibit a transient increase in the corresponding degradation coefficient. Our model and analysis allow inference of the kinetics of mRNA translation and protein degradation, without perturbing cells, and open a way to understanding the fundamental processes governing time-dependent protein abundance profiles.
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Golan-Lavi
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Giacomelli
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Garold
authors.initials: G
authors.lastname: Fuks
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Zeisel
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Sonntag
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Sanchari
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Köstler
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiemann
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Korf
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: yosef.yarden@weizmann.ac.il.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: eytan.domany@weizmann.ac.il.
authors.forename: Eytan
authors.initials: E
authors.lastname: Domany
mesh_terms: D003198:Computer Simulation; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D017781:Genes, Immediate-Early; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D010641:Phenotype; D061988:Proteasome Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D059748:Proteolysis / Q000187:drug effects*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D007976:Leupeptins; D061988:Proteasome Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012322:RNA Precursors; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: dynamic protein response; post-transcriptional processes; pulsed protein degradation