{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=curation_notes.txt"],"Pdf":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155.pdf"],"Owl":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155-biopax2.owl","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155-biopax3.owl"],"Svg":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155.svg"],"Xml":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=manifest.xml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155_url.xml"],"Other":["https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155_url.sedml","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155-octave.m","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155-matlab.m","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=metadata.rdf","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=curation_image.jpeg","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155.ode","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155.png","https://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000155?filename=BIOMD0000000155.m"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"submitter":["Harish Dharuri"],"curationStatus":["Manually curated"],"modellingApproach":["ordinary differential equation model"],"levelVersion":["L2V1"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/BIOMD0000000155"],"publication_pubmed":["16773083"],"isPrivate":["false"],"repository":["BioModels"],"non_derived_xrefs":["BIOMD0000000154 biomodels.db BIOMD0000000157 biomodels.db BIOMD0000000158 biomodels.db BIOMD0000000156 biomodels.db BIOMD0000000159 biomodels.db"],"omics_type":["Models"],"modelFormat":["SBML"],"tokenised_name":["Zatorsky2006 p53 Model6"],"publication_year":["2006"],"submissionId":["MODEL0076407823"],"first_author":["Naama Geva-Zatorsky"],"publication_authors":["Naama Geva-Zatorsky, Nitzan Rosenfeld, Shalev Itzkovitz, Ron Milo, Alex Sigal, Erez Dekel, Talia Yarnitzky, Yuvalal Liron, Paz Polak, Galit Lahav, Uri Alon"],"publication":["16773083,\n                            Understanding the dynamics and variability of protein circuitry requires accurate measurements in living cells as well as theoretical models. To address this, we employed one of the best-studied protein circuits in human cells, the negative feedback loop between the tumor suppressor p53 and the oncogene Mdm2. We measured the dynamics of fluorescently tagged p53 and Mdm2 over several days in individual living cells. We found that isogenic cells in the same environment behaved in highly variable ways following DNA-damaging gamma irradiation: some cells showed undamped oscillations for at least 3 days (more than 10 peaks). The amplitude of the oscillations was much more variable than the period. Sister cells continued to oscillate in a correlated way after cell division, but lost correlation after about 11 h on average. Other cells showed low-frequency fluctuations that did not resemble oscillations. We also analyzed different families of mathematical models of the system, including a novel checkpoint mechanism. The models point to the possible source of the variability in the oscillations: low-frequency noise in protein production rates, rather than noise in other parameters such as degradation rates. This study provides a view of the extensive variability of the behavior of a protein circuit in living human cells, both from cell to cell and in the same cell over time.. null, 2.\n                            Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel."],"submitter_mail":["hdharuri@cds.caltech.edu"],"submitter_affiliation":["California Institute of Technology"],"publicationId":["BIOMD0000000155"],"pubmed_abstract":["Understanding the dynamics and variability of protein circuitry requires accurate measurements in living cells as well as theoretical models. To address this, we employed one of the best-studied protein circuits in human cells, the negative feedback loop between the tumor suppressor p53 and the oncogene Mdm2. We measured the dynamics of fluorescently tagged p53 and Mdm2 over several days in individual living cells. We found that isogenic cells in the same environment behaved in highly variable ways following DNA-damaging gamma irradiation: some cells showed undamped oscillations for at least 3 days (more than 10 peaks). The amplitude of the oscillations was much more variable than the period. Sister cells continued to oscillate in a correlated way after cell division, but lost correlation after about 11 h on average. Other cells showed low-frequency fluctuations that did not resemble oscillations. We also analyzed different families of mathematical models of the system, including a novel checkpoint mechanism. The models point to the possible source of the variability in the oscillations: low-frequency noise in protein production rates, rather than noise in other parameters such as degradation rates. This study provides a view of the extensive variability of the behavior of a protein circuit in living human cells, both from cell to cell and in the same cell over time."],"pubmed_title":["Oscillations and variability in the p53 system."],"pubmed_authors":["Geva-Zatorsky Naama N, Rosenfeld Nitzan N, Itzkovitz Shalev S, Milo Ron R, Sigal Alex A, Dekel Erez E, Yarnitzky Talia T, Liron Yuvalal Y, Polak Paz P, Lahav Galit G, Alon Uri U"],"pubmed_abstract_synonyms":["biochemical pathways, dmBest1, dp53, PNT-P1, DmelCG17077, Addresses, Longterm., Phases, EY3-1, protein, Pnt, betaTub3, DmelCG6264, Tp53, Divisions, Long Term, dmTAF[[II]]230, Readability, DMP53, png, bbl, ARB, 1, Impacts, cellular degradation, Dmp53, Environmental Impacts, D-ets-2, 3520, protein aggregate, Effect, BEST1_HUMAN, Pnt-P1, average, 1323/07, thymus nucleic acid, me75, M Phases, Man (Taxonomy), TFIID TAF250, pre-mortem, BCC7, cel, catabolism, M, Iprit, beta-Tub6D, dmp53, T, DmP53, 1422/04, D17Mit170, T1, Division 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TAF230, beta[[3]]-Tub, DmelCG17117, 0998/12, d230, human being, DNS, p50, (Deoxyribonucleotide)n, Effects, ACTFS, Processes, ETS2, BEST1, p53, Ets2, Gene, dTAFII250, 143391_i_at, beta3 TU, Yperite, protein-containing complex, anon-WO0118547.380, LFS1, EfW1, cellular catabolism, l(3)05745, Deoxyribonucleic acids, Human, DMPOINT1A, pntegfr, 0608/07, Homo sapiens, Deoxyribonucleic Acid, dmTAF1, Taf230, 1700007J15Rik, Gene Products, Mustard gas, Low, anon-EST:Liang-2.13, 1'-thiobis(2-chloroethane), Man, TAF250, RING-type E3 ubiquitin transferase Mdm2, Brothers, study, Taf200, anatomical systems, dTAF[[II]]250, clone 2.13, Cell Division Phase, pointed-RC, occurrence, breakdown of chemical, Longterm, cell, VMD2, D.m.BETA-60D, Antigen NY-CO-13, anon-WO0118547.126, hdm2, prevalence, Double Stranded, Taf1p, Deoxyribonucleic acid, Cell Division, BMD, Long-Term, growl, Division, EK3-2, Phosphoprotein p53, bis(2-chloroethyl) sulphide, Lost, l(3)07825, dTAF250, Trp53, betaTub60C, beta3-tubulin, CG17077, DmelCG14648, Long-Term Effect, beta[[3]]-tubulin, (Deoxyribonucleotide)m, TRP53, MDM2, Behaviors, TAF, l(3)j1B7, incidence, sulfur mustard, RP50, vitelliform macular dystrophy 2 (Best disease, beta-Tub60D, cellular breakdown, oncoprotein Mdm2, Ets, TAF[[II]]250, HDMX, Dmbeta3, Dm-HTH, cou, 1-chloro-2-[(2-chloroethyl)thio]ethane, degradation, protein complex, DNAn+1, BETA 60D, Proteins, prac, beta3t, beta3-Tub, l(3)84Ab, BG:DS00004.13, Cell, nev, Xp53, Impact, dTAF230, Environmental, Lr, native protein, Period, p230, p53/tubulin, Protein, Long Term Effects, TAF[[II]]250/230, TFIID, beta[[3]] tubulin, ds-DNA, M Phase, pnt-P1, outbreaks, pnt-P2, bestrophin), l(3)s118306, breakdown of molecule, Taf[[II]]250, CG33336, Acceptance, Phase, Dbest, TAF[[II]]230, biodegradation, best, Sibling, D-p53, beta60C, Senfgas, AA415488, Dm-P53, l(3)86Ca, TAF[II]250, Mdm-2, beta3, Understanding, Sister, dtl, endemics, Noises, Longterm Effects, Protein Gene Products, Tub, Gene Proteins, Meis1, breakdown of substance, Ets58AB, DmelCG17603, betatub60D, Modern Man, Environments, Desoxyribonukleinsaeure, Bra, epidemics, variable, BEST, POINT, CG8705, TAF1"],"description_synonyms":["extent, Decidual protein induced by progesterone, Sectors, Public Sectors, Papers, YB, completeness, DmelCG2706, AUTSX5, number, DXS648, Copyrights, NOVH, CCN3, 2210402P09Rik, QM, presence., Fasting-induced gene protein, count in organism, Yb, IGFBP-9, Public, Public Domain, Figs, CAL, Domains, NOV, Public Enterprise, Enterprises, PlexA1, GOPC1, CG2706, Domain, fs(1)M104, Data Base, PIST, DmelCG7615, Plxn1, Public Domains, AI844555, nov, IGFBP9, Public Enterprises, mKIAA4053, fs(1)Y[b], dJ94G16.2, DEPP, Rubberplants, IBP-9, Kiaa4053, FIG, Fig, Sector, Rubberplant, L10, C130088N23Rik, Fseg, EG:95B7.8, CG7615, 2600013D04Rik, PLXN1, DXS648E, NOVh, Enterprise"],"pubmed_title_synonyms":["beta-Tub60D, beta[[3]]-Tub, CG10873, DmelCG17117, dp53, Dmbeta3, Dm-HTH, p50, p53, BETA 60D, prac, beta3t, beta3-Tub, 143391_i_at, beta3 TU, LFS1, betaTub3, Tp53, l(3)05745, Xp53, 3t, DMP53, bbl, p53/tubulin, Dmp53, bfy, beta[[3]] tubulin, anon-EST:Liang-2.13, Tub60D, HTH, Hth, CG33336, beta-tub, 1323/07, clone 2.13, BCC7, D.m.BETA-60D, beta-Tub6D, dmp53, DmelCG33336, D-p53, beta60C, CG3401, beta3Tub, beta3TUB, T, DmP53, Dm-P53, l(3)86Ca, 1422/04, beta3, dtl, Tub, DTB3, B3t, Meis1, DmelCG3401, hth1, Trp53, hth2, Dp53, betatub60D, P53, betaTub60C, p44, bhy, beta3-tubulin, beta[[3]]-tubulin, TRP53, anatomical systems., CG17117, CG31325, betaTub, p50/tubulin"],"additional_accession":[]},"is_claimable":false,"name":"Zatorsky2006_p53_Model6","description":"\n      \n        The model reproduces Fig 6B of the paper for model 6. The model was reproduced using XPP.\n            \n            To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to      CC0 Public Domain Dedication\n          for more information.      \n            In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.\n            \n            To cite BioModels Database, please use:      Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.\n                \n            \n      \n    ","dates":{"last_modification":"2024-08-21","publication":"2024-09-02","submission":"2008-01-14"},"accession":"BIOMD0000000155","cross_references":{"kegg__pathway":["hsa04115"],"pubmed":["16773083"],"biomodels__db":["MODEL0076407823","BIOMD0000000155"],"go":["GO:0030330","GO:0006412","GO:0042176","GO:0044257"],"taxonomy":["9606"],"bto":["BTO:0000093"],"uniprot":["P04637","Q00987"]}}