BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=curation_image.jpeghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109-matlab.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=metadata.rdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000109?filename=BIOMD0000000109.odeprimaryOK200Enuo HeManually curatedordinary differential equation modelL2V1https://www.ebi.ac.uk/biomodels/BIOMD000000010917299420falseBioModelsSBMLModelsHaberichter2007 cellcycle2007MODEL3734058719Thomas Haberichter, Britta Mädge, Renee A Christopher, Naohisa Yoshioka, Anjali Dhiman, Robert Miller, Rina Gendelman, Sergej V Aksenov, Iya G Khalil, Steven F DowdyThomas Haberichter17299420, The current dogma of G(1) cell-cycle progression relies on growth factor-induced increase of cyclin D:Cdk4/6 complex activity to partially inactivate pRb by phosphorylation and to sequester p27(Kip1)-triggering activation of cyclin E:Cdk2 complexes that further inactivate pRb. pRb oscillates between an active, hypophosphorylated form associated with E2F transcription factors in early G(1) phase and an inactive, hyperphosphorylated form in late G(1), S and G(2)/M phases. However, under constant growth factor stimulation, cells show constitutively active cyclin D:Cdk4/6 throughout the cell cycle and thereby exclude cyclin D:Cdk4/6 inactivation of pRb. To address this paradox, we developed a mathematical model of G(1) progression using physiological expression and activity profiles from synchronized cells exposed to constant growth factors and included a metabolically responsive, activating modifier of cyclin E:Cdk2. Our mathematical model accurately simulates G(1) progression, recapitulates observations from targeted gene deletion studies and serves as a foundation for development of therapeutics targeting G(1) cell-cycle progression.. null, 3. Gene Network Sciences Inc., Cambridge, MA 02141, USA.enuo.he@wolfson.ox.ac.ukUniversity of OxfordBIOMD0000000109The current dogma of G(1) cell-cycle progression relies on growth factor-induced increase of cyclin D:Cdk4/6 complex activity to partially inactivate pRb by phosphorylation and to sequester p27(Kip1)-triggering activation of cyclin E:Cdk2 complexes that further inactivate pRb. pRb oscillates between an active, hypophosphorylated form associated with E2F transcription factors in early G(1) phase and an inactive, hyperphosphorylated form in late G(1), S and G(2)/M phases. However, under constant growth factor stimulation, cells show constitutively active cyclin D:Cdk4/6 throughout the cell cycle and thereby exclude cyclin D:Cdk4/6 inactivation of pRb. To address this paradox, we developed a mathematical model of G(1) progression using physiological expression and activity profiles from synchronized cells exposed to constant growth factors and included a metabolically responsive, activating modifier of cyclin E:Cdk2. Our mathematical model accurately simulates G(1) progression, recapitulates observations from targeted gene deletion studies and serves as a foundation for development of therapeutics targeting G(1) cell-cycle progression.A systems biology dynamical model of mammalian G1 cell cycle progression.Haberichter Thomas T, Mädge Britta B, Christopher Renee A RA, Yoshioka Naohisa N, Dhiman Anjali A, Miller Robert R, Gendelman Rina R, Aksenov Sergej V SV, Khalil Iya G IG, Dowdy Steven F SFl(2)k06503, CDC2A, Forms, CDC2C, Activity, single-organism developmental process, Theoretical Model, fond, postnatal development, Addresses, cdk4/6, growth and development, RBF, CycEI, Foundation, phosphorylation, Mathematical Models, dmTAF[[II]]230, CDC2c, p27-Kip1, Ccne, cdk, Cdc2c, RB, rb, 1, rbf, Fs(3)Hor, Transcription Factors, gene expression, Progression, Cell Division Cycles, Targeting, Growth, DmelCG2684, Theoretical Study, TFIID TAF250, CDKA1, cel, pp110, Rb, Exclusion, Deletions, NTef2, Peptide Factors, Type D Cyclins, Synchronization, dCdk2, Cell Cycles, Cyclins, dCdk4, Therapies, CG7413, Paracrine, INCREASED, Therapy, CDKN1B, dTAF[[II]]230, D Cyclins, Disease Progression., Cyclin-Dependent Kinase Inhibitor 1B, rbf1, TAF200, TAFII-250, TAF250/230, Cyc E, br37, Inactivate, Division Cycles, Fs(3)Sz11, Gene Expression, Electrical Current, TAFII250, Induction, Experimental, BG:DS07108.3, Tumor Progression, CURRENT, Disease Progression, Theoretical Studies, DmCdc2, l(2)05206, activation, cell division control 2, pRb, p27Kip1, Paracrine Peptide Factors, Transcription Factor E2F, Factors, DmelCG7413, Stimulation, Type D, Division Cycle, Cancer Disease Progression, p33(CDK2), E2F Transcription Factor, Cdk4/6, DmelCG10498, exposed, CG17603, TAF[[II]], Treatments, early, E2F Transcription, Theoretical Models, p105-Rb, Stimulating, CDK4/6, l35Dd, Taf250, Expressed, SR3-5, Horka, Complexes, CG2684, l(2)0671, Fs(3)Horka, disease characteristic, EG:34F3.3, Mathematical Model, TAF230, Rbf1, RBF1, hyperphosphorylated, CDKN2, Induced, d230, cycline, Type D Cyclin, FBF, Experimental Models, DmcyclinE, Gene, dTAFII250, cycE, Pk?7, EfW1, Transcription Factor, dRBF, l(2)br37, Theoretical, Gene Deletions, CYCLE, Inducible, cdi7, Growth Factors, cyclinE, dmTAF1, Taf230, Cycle, Cdi7, CDI7, OSRC, Studies, Paracrine Protein Factors, Experimental Model, Growth Factor, DmF2, Stimulated, qualifier, Models, Current, TAF250, lod, Cycles, Taf200, dTAF[[II]]250, CYCE, disease progression, cell, CG5072, DmelCG3938, CyclE, Complex, Cell Division Cycle, Inducing, cell-division cycle, Target, 3938, P34CDC2, Synchronized, Taf1p, Cell Division, E2F, E2F Proteins, Deletion, DmcycE, Theoretic, Excluded, Heightened, l(2)k05007, Study, dTAF250, dm-cycE, cdk4, extruding from, cdk2, CDKA, Mathematical, Cyclin-Dependent Kinase Inhibitor p27, Type, CDK4, Expression, CDK2, Cdk2, TAF, Model, l(2)05428, D Cyclin, TAF[[II]]250, modifier, Inactivation, exits through, Synchronous, Phosphorylations, Targeted, l(3)84Ab, Model (Theoretical), BG:DS00004.13, Factor, Qualifier, Cell, dTAF230, l(2)s4639, development, A630093N05Rik, l(2)k02514, DmCycE, pp105, p230, TAF[[II]]250/230, PPP1R130, TFIID, CyeE, Induce, DmCdk2, DmCdk4, disease qualifier, Taf[[II]]250, Destination, CG10498, Dmcdc2c, Exclude, CYCLIN-DEPENDENT KINASE A, TAF[[II]]230, l(2)k02602, Cyclin, progression, eg1, l(2)35Dd, Increased, postnatal growth, Rb-1, CDK2/CDC2c, TAF[II]250, CDC2AAT, DmelCG5072, Lds, Modifier, Rb1, 8-6, D-CycE, Dcdc2c, Models (Theoretical), DmelCG17603, Cancer Progression, Therapeutic, Increase, S(Sev-CycE)3A, p27(KIP1), Pk53C, Treatment, RbF, responsive, CG3938, growth, General activity, l(2)sh0671, TAF1extent, phapii, IPP2A2, Sectors, Public Sectors, Papers, YB, completeness, DmelCG2706, AUTSX5, igaad, number, StF-IT-1, DXS648, Copyrights, NOVH, CCN3, QM, Cell, Division Cycles, PHAPII, group, presence., 5730420M11Rik, count in organism, Yb, I-2PP2A, IGFBP-9, Public, Public Domain, Systems, Cycle, Dm I-2, I2PP2A, Domains, NOV, Public Enterprise, Enterprises, PlexA1, CG2706, Domain, fs(1)M104, Data Base, Cell Division Cycles, Cycles, SET, Plxn1, HLA-DR-associated protein II, Biology, Division Cycle, ensemble, DI-2, TAF-I, I-2Dm, ipp2a2, Public Domains, Cell Division Cycle, cell-division cycle, 2pp2a, nov, Cell Division, CG4299, IGFBP9, Public Enterprises, mKIAA4053, CG10574, fs(1)Y[b], DmelCG4299, I-2PP1, IBP-9, IGAAD, set, dSET/TAF-Ibeta, Kiaa4053, 2610030F17Rik, Sector, TAF-IBETA, 2PP2A, DmelCG10574, taf-ibeta, L10, C130088N23Rik, Cell Cycles, EG:95B7.8, dSET, dSet, 2600013D04Rik, TAF-Ibeta, PLXN1, DXS648E, NOVh, Enterprise, AA407739, i2pp2aMammal, Mammalia, General, Biology, Mammals, Systems, Cell Cycle Progression., MammalianfalseHaberichter2007_cellcycle This model is according to the paper A systems biology dynamical model of mammalian G1 cell cycle progression. Supplementary Figure 2A has been reproduced by the MathSBML and CellDesigner. All the data of this model are from the set 2 of Supplementary talbe2. 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 for more information. 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. 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. 2024-08-212024-09-022007-04-17BIOMD0000000109hsa0411017299420MODEL3734058719BIOMD0000000109GO:0043241GO:0004861GO:0006461GO:0051318GO:0005623GO:0005680GO:0032147GO:0045737GO:0016311GO:0035189GO:0005515GO:0009058GO:0044257GO:0004693GO:000641240674Q9UJX6P06493P24941Q9UKT4P06400P24864P30285Q5SCB5IPR015453IPR015456IPR015633