meta r14
kinetic law: 068262
reactant: 068250
notes: CycD decay
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
type: Reaction

854600
is: SBO:0000356
units: 067709
value: 1.5
type: LocalParameter

854583
is: SBO:0000027
units: 067673
value: 0.92
type: LocalParameter

854593
is: SBO:0000025
units: 067709
value: 18.0
type: LocalParameter

068371
persistant: true
initial value: true
type: Trigger

067574
unit: 067587
name: micromole
type: SBMLUnitsDef

067637
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

meta r5
modifier: 067913
kinetic law: 067925
type: Reaction
fast: false
notes: CycD synthesis driven by Myc
product: 067901
reversible: false
is version of: GO:0031659
is: SBO:0000205

068226
stoichiometry: 1.0
species: meta CE
type: SpeciesReference

meta cell
is: GO:0005622
is: SBO:0000290
constant: true
size: 1.0
spatial dimensions: 3.0
name: cell
type: Compartment

meta EF
constant: false
is homolog to: Q01094
initial amount: NaN
in compartment: meta cell
type: Species
name: E2F
initial concentration: 0.0
has only substance units: false
is: SBO:0000252
boundary condition: false

067721
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

067685
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

067865
stoichiometry: 1.0
species: meta CE
type: SpeciesReference

854582
is: SBO:0000048
units: 067624
value: 0.18
type: LocalParameter

854592
is: SBO:0000025
units: 067709
value: 18.0
type: LocalParameter

854607
event assignment: 068383
trigger: 068371
use values from trigger time: true
type: Event

meta r13
kinetic law: 068238
reactant: 068226
notes: CycE decay
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
type: Reaction

meta r4
type: Reaction
notes: CycE synthesis driven by E2F
is: SBO:0000205
kinetic law: 067889
product: 067865
modifier: 067877
is version of: GO:0031659
fast: false
reversible: false

854572
is: SBO:0000186
units: 067624
value: 0.003
type: LocalParameter

067769
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

068141
stoichiometry: 1.0
species: meta RP
type: SpeciesReference

068093
stoichiometry: 1.0
species: meta RP
type: SpeciesReference

067781
stoichiometry: 1.0
species: meta MC
type: SpeciesReference

meta r12
kinetic law: 068214
reactant: 068202
notes: E2F decay
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
type: Reaction

854595
is: SBO:0000186
units: 067624
value: 3.6
type: LocalParameter

067901
stoichiometry: 1.0
species: meta CD
type: SpeciesReference

068250
stoichiometry: 1.0
species: meta CD
type: SpeciesReference

854606
event assignment: 068359
trigger: 068346
use values from trigger time: true
type: Event

067697
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

854589
is: SBO:0000027
units: 067673
value: 0.92
type: LocalParameter

068322
stoichiometry: 1.0
species: meta RE
type: SpeciesReference

meta r3
kinetic law: 067853
notes: E2F synthesis by a synergy between Myc and E2F autocatalysis. Since neither Myc nor E2F forms a homodimer, we assumed no cooperativity in gene activation mediated by these factors, and used the Hill coefficient of 1.0. Using Hill coefficient greater than 1.0 will not change the qualitative behavior of system dynamics
is version of: GO:0010467
type: Reaction
product: 067829
modifier: 067841
fast: false
reversible: false
is: SBO:0000205

068177
stoichiometry: 1.0
species: meta MC
type: SpeciesReference

854569
is: SBO:0000027
units: 067673
value: 0.15
type: LocalParameter

067961
stoichiometry: 1.0
species: meta RE
type: SpeciesReference

854594
is: SBO:0000027
units: 067673
value: 0.01
type: LocalParameter

meta r11
kinetic law: 068190
reactant: 068177
notes: Myc decay
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
type: Reaction

854580
is: SBO:0000186
units: 067624
value: 0.03
type: LocalParameter

068298
stoichiometry: 1.0
species: meta RP
type: SpeciesReference

854605
is: SBO:0000356
units: 067709
value: 0.03
type: LocalParameter

854588
is: SBO:0000339
units: 067733
value: 180.0
type: LocalParameter

meta r2
kinetic law: 067817
product: 067805
notes: CycD synthesis driven by growth signals
is version of: GO:0010467
is: SBO:0000205
fast: false
reversible: false
type: Reaction

067757
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

854574
is: SBO:0000027
units: 067673
value: 0.15
type: LocalParameter

067624
unit: 067661
unit: 067649
unit: 067637
name: uM per hr
type: SBMLUnitsDef

854568
is: SBO:0000027
units: 067673
value: 0.15
type: LocalParameter

meta S
notes: Serum concentration of the surrounding medium in percent, growth signal
has property: GO:0008083
is: SBO:0000472
constant: false
units: dimensionless
value: 1.0
name: S
type: Parameter

meta RE
has part: P06400
constant: false
has part: Q01094
type: Species
name: Rb-E2F complex
is: SBO:0000297
has only substance units: false
initial amount: NaN
in compartment: meta cell
initial concentration: 0.55
boundary condition: false

067973
stoichiometry: 1.0
species: meta EF
type: SpeciesReference

068033
stoichiometry: 1.0
species: meta EF
type: SpeciesReference

meta r9
modifier: 068117
is version of: GO:0006468
is version of: http://identifiers.org/ec-code/2.7.11.22
notes: Rb phosphorylation by CycD and CycE
reversible: false
product: 068093
kinetic law: 068129
reactant: 068081
is: SBO:0000216
modifier: 068105
type: Reaction
fast: false

meta r10
product: 068153
fast: false
reversible: false
reactant: 068141
is version of: GO:0006470
type: Reaction
notes: Rb dephosphorylation
kinetic law: 068165
is: SBO:0000330

854567
is: SBO:0000186
units: 067624
value: 0.45
type: LocalParameter

meta r1
kinetic law: 067793
product: 067781
notes: Myc synthesis driven by growth signals (S)
is version of: GO:0010467
is: SBO:0000205
fast: false
reversible: false
type: Reaction

067937
stoichiometry: 1.0
species: meta RB
type: SpeciesReference

meta r15
kinetic law: 068286
reactant: 068274
notes: Rb decay
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
type: Reaction

854590
is: SBO:0000027
units: 067673
value: 0.92
type: LocalParameter

067587
exponent: 1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

854566
is: SBO:0000027
units: dimensionless
value: 0.5
type: LocalParameter

067745
exponent: -1.0
scale: -6
multipler: 1.0
kind: MOLE
type: SBMLUnit

854596
is: SBO:0000356
units: 067709
value: 0.7
type: LocalParameter

meta r8
kinetic law: 068069
is version of: GO:0006461
fast: false
reactant: 068033
reversible: false
type: Reaction
notes: E2F titration by Rb via E2F-Rb complex formation
product: 068057
is: SBO:0000177
reactant: 068045

067649
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

067661
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

067805
stoichiometry: 1.0
species: meta CD
type: SpeciesReference

854576
is: SBO:0000186
units: 067624
value: 0.35
type: LocalParameter

854586
is: SBO:0000025
units: 067709
value: 18.0
type: LocalParameter

067612
exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

meta r16
kinetic law: 068310
reactant: 068298
notes: Phosphorylated Rb decay
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
type: Reaction

854603
is: SBO:0000356
units: 067709
value: 0.06
type: LocalParameter

068045
stoichiometry: 1.0
species: meta RB
type: SpeciesReference

meta r7
kinetic law: 068021
product: 067985
reactant: 067961
reversible: false
is: SBO:0000180
has version: GO:0043241
modifier: 067997
product: 067973
notes: E2F dissociation from Rb-E2F complex by CycD- and CycE-mediated phosphorylation
has version: GO:0004693
modifier: 068009
has version: http://identifiers.org/ec-code/2.7.11.22
fast: false
type: Reaction

854565
is: SBO:0000186
units: 067624
value: 1.0
type: LocalParameter

068346
persistant: true
initial value: true
type: Trigger

854599
is: SBO:0000356
units: 067709
value: 1.5
type: LocalParameter

meta CE
initial concentration: 0.0
type: Species
initial amount: NaN
is version of: GO:0000307
has only substance units: false
in compartment: meta cell
boundary condition: false
name: CycE
constant: false
has property: GO:0004693
has version: P24864
has version: O96020
is: SBO:0000252

meta RB
name: Rb
initial amount: NaN
constant: false
has only substance units: false
type: Species
in compartment: meta cell
boundary condition: false
is homolog to: P06400
initial concentration: 0.0
is: SBO:0000252

067829
stoichiometry: 1.0
species: meta EF
type: SpeciesReference

068081
stoichiometry: 1.0
species: meta RB
type: SpeciesReference

067985
stoichiometry: 1.0
species: meta RP
type: SpeciesReference

854602
is: SBO:0000356
units: 067709
value: 0.06
type: LocalParameter

meta MC
in compartment: meta cell
boundary condition: false
type: Species
constant: false
is homolog to: P01106
initial concentration: 0.0
is: SBO:0000252
initial amount: NaN
name: Myc
has only substance units: false

meta r17
kinetic law: 068334
reactant: 068322
notes: Rb-E2F complex decay
is version of: GO:0030163
is: SBO:0000179
fast: false
reversible: false
type: Reaction

meta RP
initial amount: NaN
has only substance units: false
boundary condition: false
has property: MOD:00046
type: Species
constant: false
in compartment: meta cell
is homolog to: P06400
is: SBO:0000252
initial concentration: 0.0
name: phosphorylated Rb
is version of: C00562

067673
unit: 067697
unit: 067685
name: uM
type: SBMLUnitsDef

068153
stoichiometry: 1.0
species: meta RB
type: SpeciesReference

854564
is: SBO:0000027
units: dimensionless
value: 0.5
type: LocalParameter

068057
stoichiometry: 1.0
species: meta RE
type: SpeciesReference

067600
unit: 067612
name: hour
type: SBMLUnitsDef

854598
is: SBO:0000356
units: 067709
value: 0.25
type: LocalParameter

meta CD
in compartment: meta cell
boundary condition: false
is: SBO:0000252
has version: IPR015451
type: Species
has property: GO:0004693
initial amount: NaN
has only substance units: false
initial concentration: 0.0
is version of: GO:0000307
constant: false
name: CycD

068202
stoichiometry: 1.0
species: meta EF
type: SpeciesReference

BIOMD0000000318
event: 854607
is part of: REACT 1783.2
length unit: length
is described by: http://identifiers.org/pubmed/18364697
event: 854606
modified:
  W3 CDTF: Thu Jul 05 15:47:58 BST 2012
reaction: meta r6
units def: 067574
is part of: GO:2000045
is: MODEL1102090000
occurs in: http://identifiers.org/taxonomy/40674
reaction: meta r1
time units: 067600
name: Yao2008_Rb_E2F_Switch
reaction: meta r10
volume units: 670980
curated: true
reaction: meta r16
reaction: meta r15
notes: This is the model described in the article: A bistable Rb-E2F switch underlies the restriction point Guang Yao, Tae Jun Lee, Seiichi Mori, Joseph R. Nevins, Lingchong You, Nat Cell Biol 2008 10:476-482; PMID: 18364697 ; DOI: 10.1038/ncb1711 . Abstract: The restriction point (R-point) marks the critical event when a mammalian cell commits to proliferation and becomes independent of growth stimulation. It is fundamental for normal differentiation and tissue homeostasis, and seems to be dysregulated in virtually all cancers. Although the R-point has been linked to various activities involved in the regulation of G1-S transition of the mammalian cell cycle, the underlying mechanism remains unclear. Using single-cell measurements, we show here that the Rb-E2F pathway functions as a bistable switch to convert graded serum inputs into all-or-none E2F responses. Once turned ON by sufficient serum stimulation, E2F can memorize and maintain this ON state independently of continuous serum stimulation. We further show that, at critical concentrations and duration of serum stimulation, bistable E2F activation correlates directly with the ability of a cell to traverse the R-point. This model reproduces the serum-pulse stimulation-protocol in Figure 3(b). 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 Novere N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative k…
species: meta EF
units def: 067733
reaction: meta r3
reaction: meta r2
area units: area
species: meta CE
has version: GO:0000083
units def: 067709
reaction: meta r7
species: meta MC
reaction: meta r12
species: meta RE
reaction: meta r11
units def: 067600
type: SBMLModel
creator:
  ORG:
    orgname: University of Manchester
  n:
    given: Kieran
    family: Smallbone
substance units: 067574
species: meta RP
reaction: meta r17
parameter: meta S
units def: 067624
reaction: meta r5
reaction: meta r4
created:
  W3 CDTF: Tue Feb 08 00:00:00 GMT 2011
species: meta RB
reaction: meta r9
species: meta CD
reaction: meta r8
reaction: meta r14
reaction: meta r13
compartment: meta cell
units def: 067673

854578
is: SBO:0000027
units: 067673
value: 0.15
type: LocalParameter

067733
unit: 067769
unit: 067757
unit: 067745
name: per_uM per hr
type: SBMLUnitsDef

854584
is: SBO:0000027
units: 067673
value: 0.92
type: LocalParameter

854570
is: SBO:0000186
units: 067624
value: 0.4
type: LocalParameter

068274
stoichiometry: 1.0
species: meta RB
type: SpeciesReference

067709
unit: 067721
name: per hr
type: SBMLUnitsDef

meta r6
kinetic law: 067949
product: 067937
notes: Constitutive Rb synthesis
is version of: GO:0010467
is: SBO:0000205
fast: false
reversible: false
type: Reaction