BioModels Database logo

BioModels Database

spacer

BIOMD0000000318 - Yao2008_Rb_E2F_Switch

 

 |   |   |  Send feedback
Reference Publication
Publication ID: 18364697
Yao G, Lee TJ, Mori S, Nevins JR, You L.
A bistable Rb-E2F switch underlies the restriction point.
Nat. Cell Biol. 2008 Apr; 10(4): 476-482
Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.  [more]
Model
Original Model: BIOMD0000000318.xml.origin
Submitter: Kieran Smallbone
Submission ID: MODEL1102090000
Submission Date: 09 Feb 2011 14:40:44 UTC
Last Modification Date: 31 Mar 2014 12:24:34 UTC
Creation Date: 08 Feb 2011 00:00:00 UTC
Encoders:  Kieran Smallbone
set #1
bqbiol:hasTaxon Taxonomy Mammalia
bqbiol:hasVersion Gene Ontology regulation of transcription involved in G1/S transition of mitotic cell cycle
bqbiol:isPartOf Gene Ontology regulation of G1/S transition of mitotic cell cycle
set #2
bqbiol:isPartOf Reactome REACT_1783.2
set #3
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
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 kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 18364697 Submission Date: 09 Feb 2011 14:40:44 UTC Last Modification Date: 31 Mar 2014 12:24:34 UTC Creation Date: 08 Feb 2011 00:00:00 UTC
Mathematical expressions
Reactions
r1 r2 r3 r4
r5 r6 r7 r8
r9 r10 r11 r12
r13 r14 r15 r16
r17      
Events
e1 e2    
Physical entities
Compartments Species
cell Myc E2F CycD
CycE Rb Rb-E2F complex
phosphorylated Rb    
Global parameters
S      
Reactions (17)
 
 r1  → [Myc];  
 
 r2  → [CycD];  
 
 r3  → [E2F];   {Myc}
 
 r4  → [CycE];   {E2F}
 
 r5  → [CycD];   {Myc}
 
 r6  → [Rb];  
 
 r7 [Rb-E2F complex] → [E2F] + [phosphorylated Rb];   {CycD} , {CycE}
 
 r8 [E2F] + [Rb] → [Rb-E2F complex];  
 
 r9 [Rb] → [phosphorylated Rb];   {CycD} , {CycE}
 
 r10 [phosphorylated Rb] → [Rb];  
 
 r11 [Myc] → ;  
 
 r12 [E2F] → ;  
 
 r13 [CycE] → ;  
 
 r14 [CycD] → ;  
 
 r15 [Rb] → ;  
 
 r16 [phosphorylated Rb] → ;  
 
 r17 [Rb-E2F complex] → ;  
 
Events (2)
 
 e1
S = 20
 
 e2
S = 1
 
 cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 Myc
Compartment: cell
Initial concentration: 0.0
 
 E2F
Compartment: cell
Initial concentration: 0.0
 
 CycD
Compartment: cell
Initial concentration: 0.0
 
 CycE
Compartment: cell
Initial concentration: 0.0
 
 Rb
Compartment: cell
Initial concentration: 0.0
 
 Rb-E2F complex
Compartment: cell
Initial concentration: 0.55
 
 phosphorylated Rb
Compartment: cell
Initial concentration: 0.0
 
Global Parameters (1)
 
 S
Value: 1.0   (Units: dimensionless)
 
r1 (2)
 
 KS
Value: 0.5   (Units: dimensionless)
Constant
 
 kM
Value: 1.0   (Units: uM per hr)
Constant
 
r2 (2)
 
 KS
Value: 0.5   (Units: dimensionless)
Constant
 
 kkCDS
Value: 0.45   (Units: uM per hr)
Constant
 
r3 (4)
 
 KEF
Value: 0.15   (Units: uM)
Constant
 
 KMC
Value: 0.15   (Units: uM)
Constant
 
 kkEF
Value: 0.4   (Units: uM per hr)
Constant
 
 kkb
Value: 0.0030   (Units: uM per hr)
Constant
 
r4 (2)
 
 KEF
Value: 0.15   (Units: uM)
Constant
 
 kkCE
Value: 0.35   (Units: uM per hr)
Constant
 
r5 (2)
 
 KMC
Value: 0.15   (Units: uM)
Constant
 
 kkCD
Value: 0.03   (Units: uM per hr)
Constant
 
r6 (1)
 
 kkRB
Value: 0.18   (Units: uM per hr)
Constant
 
r7 (3)
 
 KD
Value: 0.92   (Units: uM)
Constant
 
 KE
Value: 0.92   (Units: uM)
Constant
 
 kkRBPP
Value: 18.0   (Units: per hr)
Constant
 
r8 (1)
 
 kkRE
Value: 180.0   (Units: per_uM per hr)
Constant
 
r9 (4)
 
 KD
Value: 0.92   (Units: uM)
Constant
 
 KE
Value: 0.92   (Units: uM)
Constant
 
 kkRBP
Value: 18.0   (Units: per hr)
Constant
 
 kkRBP2
Value: 18.0   (Units: per hr)
Constant
 
r10 (2)
 
 Kp
Value: 0.01   (Units: uM)
Constant
 
 kkRBUP
Value: 3.6   (Units: uM per hr)
Constant
 
r11 (1)
 
 dMC
Value: 0.7   (Units: per hr)
Constant
 
r12 (1)
 
 dEF
Value: 0.25   (Units: per hr)
Constant
 
r13 (1)
 
 dCE
Value: 1.5   (Units: per hr)
Constant
 
r14 (1)
 
 dCD
Value: 1.5   (Units: per hr)
Constant
 
r15 (1)
 
 dRB
Value: 0.06   (Units: per hr)
Constant
 
r16 (1)
 
 dRP
Value: 0.06   (Units: per hr)
Constant
 
r17 (1)
 
 dRE
Value: 0.03   (Units: per hr)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000318

Curator's comment: (updated: 03 May 2011 12:10:18 BST)

Bifurcation diagram as in fig. 1B of the original publication. The diagram was computed using SBW and its Auto2000 frontend (http://sys-bio.org/fbergman/files/latest/SetupAutoWrapper.exe) and gnuplot.

spacer
spacer