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aguda_b_1999.cellml
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<?xml version="1.0"?>
<!--
This CellML file was generated on 10/03/2009 at 12:46:07 at p.m. using:
COR (0.9.31.1175)
Copyright 2002-2009 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - [email protected]
CellML 1.0 was used to generate this model
http://www.CellML.org/
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" cmeta:id="aguda_1999_b_version01" name="aguda_1999_b_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A quantitative analysis of the kinetics of the G2 DNA damage checkpoint system</title>
<author>
<firstname>Jeelean</firstname>
<surname>Lim</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML version of the models runs in PCEnv to reproduce the results shown in figure 8 of the published paper. Units have been checked and are consistent.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: A detailed model of the G2 DNA damage checkpoint (G2DDC) system is presented that includes complex regulatory networks of the mitotic kinase Cdc2, phosphatase Cdc25, Wee1 kinase, and damage signal transduction pathways involving Chk1 and p53. Assumptions on the kinetic
equations of the G2DDC are made, and computer simulations are carried out to demonstrate how the various subsystems operate to delay or arrest cell cycle progression. The detailed model could be used to explain various experiments relevant to G2DDC reported recently, including the nuclear export of 1433 bound Cdc25, the down-regulation of cyclin B1 expression by p53, the effect of Chk1 and p53 on Cdc25 levels, and Wee1 degradation. It also is shown that, under certain conditions, p53 is necessary to sustain a G2 arrest.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
A quantitative analysis of the kinetics of the G2 DNA damage checkpoint system, Baltazar D. Aguda, 1999 <emphasis>Proceedings of the National Academy of Sciences</emphasis>, 96, 11352-11357
<ulink url="http://www.ncbi.nlm.nih.gov/pubmed/10500180">PubMed ID: 10500180 </ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>Figure 1</title>
</objectinfo>
<imagedata fileref="aguda_1999_ba.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the G2DDC system showing the subsystems involving Wee1, MPF, Cdc25, and signal transduction pathways.</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>Figure 2</title>
</objectinfo>
<imagedata fileref="aguda_1999_bb.png"/>
</imageobject>
</mediaobject>
<caption>The MPF subsystem.</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>Figure 4</title>
</objectinfo>
<imagedata fileref="aguda_1999_bc.png"/>
</imageobject>
</mediaobject>
<caption>The Cdc25 subsystem.</caption>
</informalfigure>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>Figure 6</title>
</objectinfo>
<imagedata fileref="aguda_1999_bd.png"/>
</imageobject>
</mediaobject>
<caption>The Wee1 subsystem.</caption>
</informalfigure>
</sect1>
</article>
</documentation> <units name="millimolar">
<unit prefix="milli" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="minute">
<unit multiplier="60" units="second"/>
</units>
<units name="first_order_rate_constant">
<unit exponent="-1" units="minute"/>
</units>
<component name="environment">
<variable cmeta:id="environment_time" name="time" public_interface="out" units="minute"/>
</component>
<component name="rate_constants">
<variable initial_value="1" name="k1" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="10" name="kn1" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k2" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="kn2" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k2_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="100" name="k3_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="kn3_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="k4" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="k5" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="k6" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="k7" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="kn7" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k8" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="kn8" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="k8_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="k9" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="kn9" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="k9_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="k10" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="k11" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k12" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="k13" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.0005" name="k14" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="k14_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="k15" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.0002" name="k16" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k17" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="k18" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="kn18" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k20" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="k21" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k22" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k23" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="kn23" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="kPlk1" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="kPlk1_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="kctak1" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0" name="kctak1_" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1" name="kex" public_interface="out" units="first_order_rate_constant"/>
</component>
<component name="Chk1P">
<variable initial_value="0.000001" name="Chk1P" public_interface="out" units="dimensionless"/>
<variable name="V_n1" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Chk1P</ci>
</apply>
<apply>
<minus/>
<ci>V_1</ci>
<ci>V_n1</ci>
</apply>
</apply>
</math>
</component>
<component name="Rad3">
<variable initial_value="0" name="Rad3" public_interface="out" units="dimensionless"/>
<variable name="V_4" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_5" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Rad3</ci>
</apply>
<apply>
<minus/>
<ci>V_4</ci>
<ci>V_5</ci>
</apply>
</apply>
</math>
</component>
<component name="p53">
<variable initial_value="0" name="p53" public_interface="out" units="dimensionless"/>
<variable name="V_10" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_11" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>p53</ci>
</apply>
<apply>
<minus/>
<ci>V_10</ci>
<ci>V_11</ci>
</apply>
</apply>
</math>
</component>
<component name="preMPF">
<variable initial_value="0.000001" name="preMPF" public_interface="out" units="dimensionless"/>
<variable name="V_14" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n9" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_9" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>preMPF</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_14</ci>
<ci>V_n9</ci>
</apply>
<ci>V_9</ci>
</apply>
</apply>
</math>
</component>
<component name="MPF">
<variable cmeta:id="MPF_MPF" initial_value="0.00000001" name="MPF" public_interface="out" units="dimensionless"/>
<variable name="V_9" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n23" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n9" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_23" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_15" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>MPF</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_9</ci>
<ci>V_n23</ci>
</apply>
<apply>
<plus/>
<ci>V_n9</ci>
<ci>V_23</ci>
<ci>V_15</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="p21">
<variable initial_value="0" name="p21" public_interface="out" units="dimensionless"/>
<variable name="V_21" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_20" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n23" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_22" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_23" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>p21</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_20</ci>
<ci>V_21</ci>
<ci>V_n23</ci>
</apply>
<apply>
<plus/>
<ci>V_22</ci>
<ci>V_23</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="p21_MPF">
<variable initial_value="0" name="p21_MPF" public_interface="out" units="dimensionless"/>
<variable name="V_23" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n23" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>p21_MPF</ci>
</apply>
<apply>
<minus/>
<ci>V_23</ci>
<ci>V_n23</ci>
</apply>
</apply>
</math>
</component>
<component name="iCdc25">
<variable initial_value="0.000001" name="iCdc25" public_interface="out" units="dimensionless"/>
<variable name="V_n7" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_7" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_2_" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_in" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>iCdc25</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_n7</ci>
<ci>V_n3_</ci>
<ci>V_in</ci>
</apply>
<apply>
<plus/>
<ci>V_7</ci>
<ci>V_2_</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="iCdc25Ps216">
<variable initial_value="0.00002" name="iCdc25Ps216" public_interface="out" units="dimensionless"/>
<variable name="V_2_" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n18" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_18" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>iCdc25Ps216</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_2_</ci>
<ci>V_n18</ci>
</apply>
<apply>
<plus/>
<ci>V_18</ci>
<ci>V_3_</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="iCdc25Ps216_protein1433">
<variable initial_value="0.03" name="iCdc25Ps216_protein1433" public_interface="out" units="dimensionless"/>
<variable name="V_3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_ex" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>iCdc25Ps216_protein1433</ci>
</apply>
<apply>
<minus/>
<ci>V_3_</ci>
<apply>
<plus/>
<ci>V_n3_</ci>
<ci>V_ex</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="aCdc25">
<variable initial_value="0.000001" name="aCdc25" public_interface="out" units="dimensionless"/>
<variable name="V_7" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n2" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n7" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>aCdc25</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_7</ci>
<ci>V_n2</ci>
</apply>
<apply>
<plus/>
<ci>V_n7</ci>
<ci>V_2</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="aCdc25Ps216">
<variable initial_value="0" name="aCdc25Ps216" public_interface="out" units="dimensionless"/>
<variable name="V_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_18" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n2" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n18" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>aCdc25Ps216</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_2</ci>
<ci>V_18</ci>
</apply>
<apply>
<plus/>
<ci>V_n2</ci>
<ci>V_n18</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="protein1433">
<variable initial_value="2" name="protein1433" public_interface="out" units="dimensionless"/>
<variable name="V_6" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_13" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_12" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>protein1433</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_6</ci>
<ci>V_13</ci>
<ci>V_n3_</ci>
</apply>
<apply>
<plus/>
<ci>V_3_</ci>
<ci>V_12</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Wee1">
<variable cmeta:id="Wee1_Wee1" initial_value="0.001" name="Wee1" public_interface="out" units="dimensionless"/>
<variable name="V_16" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n8" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_8" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Wee1</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>V_16</ci>
<ci>V_n8</ci>
</apply>
<ci>V_8</ci>
</apply>
</apply>
</math>
</component>
<component name="Wee1P">
<variable initial_value="0" name="Wee1P" public_interface="out" units="dimensionless"/>
<variable name="V_8" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_n8" public_interface="in" units="first_order_rate_constant"/>
<variable name="V_17" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Wee1P</ci>
</apply>
<apply>
<minus/>
<ci>V_8</ci>
<apply>
<plus/>
<ci>V_n8</ci>
<ci>V_17</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="aCdc25_T">
<variable cmeta:id="aCdc25_T_aCdc25_T" name="aCdc25_T" public_interface="out" units="dimensionless"/>
<variable name="aCdc25" public_interface="in" units="dimensionless"/>
<variable name="aCdc25Ps216" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>aCdc25_T</ci>
<apply>
<plus/>
<ci>aCdc25</ci>
<ci>aCdc25Ps216</ci>
</apply>
</apply>
</math>
</component>
<component name="V_1">
<variable name="V_1" public_interface="out" units="first_order_rate_constant"/>
<variable name="k1" public_interface="in" units="first_order_rate_constant"/>
<variable name="Chk1" units="dimensionless"/>
<variable name="Chk1P" public_interface="in" units="dimensionless"/>
<variable initial_value="1" name="Chk1_T" units="dimensionless"/>
<variable name="Rad3" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Chk1</ci>
<apply>
<minus/>
<ci>Chk1_T</ci>
<ci>Chk1P</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>V_1</ci>
<apply>
<times/>
<ci>k1</ci>
<ci>Chk1</ci>
<ci>Rad3</ci>
</apply>
</apply>
</math>
</component>
<component name="V_n1">
<variable name="V_n1" public_interface="out" units="first_order_rate_constant"/>
<variable name="kn1" public_interface="in" units="first_order_rate_constant"/>
<variable name="Chk1P" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_n1</ci>
<apply>
<times/>
<ci>kn1</ci>
<ci>Chk1P</ci>
</apply>
</apply>
</math>
</component>
<component name="V_2">
<variable name="V_2" public_interface="out" units="first_order_rate_constant"/>
<variable name="k2" public_interface="in" units="first_order_rate_constant"/>
<variable name="kctak1" public_interface="in" units="first_order_rate_constant"/>
<variable name="Chk1P" public_interface="in" units="dimensionless"/>
<variable name="aCdc25" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_2</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k2</ci>
<ci>Chk1P</ci>
<ci>aCdc25</ci>
</apply>
<apply>
<times/>
<ci>kctak1</ci>
<ci>aCdc25</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_n2">
<variable name="V_n2" public_interface="out" units="first_order_rate_constant"/>
<variable name="kn2" public_interface="in" units="first_order_rate_constant"/>
<variable name="aCdc25Ps216" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_n2</ci>
<apply>
<times/>
<ci>kn2</ci>
<ci>aCdc25Ps216</ci>
</apply>
</apply>
</math>
</component>
<component name="V_2_">
<variable name="V_2_" public_interface="out" units="first_order_rate_constant"/>
<variable name="k2_" public_interface="in" units="first_order_rate_constant"/>
<variable name="kctak1_" public_interface="in" units="first_order_rate_constant"/>
<variable name="Chk1P" public_interface="in" units="dimensionless"/>
<variable name="iCdc25" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_2_</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k2_</ci>
<ci>Chk1P</ci>
<ci>iCdc25</ci>
</apply>
<apply>
<times/>
<ci>kctak1_</ci>
<ci>iCdc25</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_3_">
<variable name="V_3_" public_interface="out" units="first_order_rate_constant"/>
<variable name="k3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="iCdc25Ps216" public_interface="in" units="dimensionless"/>
<variable name="protein1433" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_3_</ci>
<apply>
<times/>
<ci>k3_</ci>
<ci>iCdc25Ps216</ci>
<ci>protein1433</ci>
</apply>
</apply>
</math>
</component>
<component name="V_n3_">
<variable name="V_n3_" public_interface="out" units="first_order_rate_constant"/>
<variable name="kn3_" public_interface="in" units="first_order_rate_constant"/>
<variable name="iCdc25Ps216_protein1433" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_n3_</ci>
<apply>
<times/>
<ci>kn3_</ci>
<ci>iCdc25Ps216_protein1433</ci>
</apply>
</apply>
</math>
</component>
<component name="V_4">
<variable name="V_4" public_interface="out" units="first_order_rate_constant"/>
<variable name="k4" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_4</ci>
<ci>k4</ci>
</apply>
</math>
</component>
<component name="V_5">
<variable name="V_5" public_interface="out" units="first_order_rate_constant"/>
<variable name="k5" public_interface="in" units="first_order_rate_constant"/>
<variable name="Rad3" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_5</ci>
<apply>
<times/>
<ci>k5</ci>
<ci>Rad3</ci>
</apply>
</apply>
</math>
</component>
<component name="V_6">
<variable name="V_6" public_interface="out" units="first_order_rate_constant"/>
<variable name="k6" public_interface="in" units="first_order_rate_constant"/>
<variable name="p53" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_6</ci>
<apply>
<times/>
<ci>k6</ci>
<ci>p53</ci>
</apply>
</apply>
</math>
</component>
<component name="V_7">
<variable name="V_7" public_interface="out" units="first_order_rate_constant"/>
<variable name="k7" public_interface="in" units="first_order_rate_constant"/>
<variable name="kPlk1" public_interface="in" units="first_order_rate_constant"/>
<variable name="MPF" public_interface="in" units="dimensionless"/>
<variable name="iCdc25" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_7</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k7</ci>
<ci>MPF</ci>
<ci>iCdc25</ci>
</apply>
<apply>
<times/>
<ci>kPlk1</ci>
<ci>iCdc25</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_n7">
<variable name="V_n7" public_interface="out" units="first_order_rate_constant"/>
<variable name="kn7" public_interface="in" units="first_order_rate_constant"/>
<variable name="aCdc25" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_n7</ci>
<apply>
<times/>
<ci>kn7</ci>
<ci>aCdc25</ci>
</apply>
</apply>
</math>
</component>
<component name="V_8">
<variable name="V_8" public_interface="out" units="first_order_rate_constant"/>
<variable name="k8" public_interface="in" units="first_order_rate_constant"/>
<variable name="k8_" public_interface="in" units="first_order_rate_constant"/>
<variable name="MPF" public_interface="in" units="dimensionless"/>
<variable name="Wee1" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_8</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k8</ci>
<ci>MPF</ci>
<ci>Wee1</ci>
</apply>
<apply>
<times/>
<ci>k8_</ci>
<ci>Wee1</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_n8">
<variable name="V_n8" public_interface="out" units="first_order_rate_constant"/>
<variable name="kn8" public_interface="in" units="first_order_rate_constant"/>
<variable name="Wee1P" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_n8</ci>
<apply>
<times/>
<ci>kn8</ci>
<ci>Wee1P</ci>
</apply>
</apply>
</math>
</component>
<component name="V_9">
<variable name="V_9" public_interface="out" units="first_order_rate_constant"/>
<variable name="k9" public_interface="in" units="first_order_rate_constant"/>
<variable name="k9_" public_interface="in" units="first_order_rate_constant"/>
<variable name="preMPF" public_interface="in" units="dimensionless"/>
<variable name="aCdc25" public_interface="in" units="dimensionless"/>
<variable name="aCdc25Ps216" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_9</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k9</ci>
<apply>
<plus/>
<ci>aCdc25</ci>
<ci>aCdc25Ps216</ci>
</apply>
<ci>preMPF</ci>
</apply>
<apply>
<times/>
<ci>k9_</ci>
<ci>preMPF</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_n9">
<variable name="V_n9" public_interface="out" units="first_order_rate_constant"/>
<variable name="kn9" public_interface="in" units="first_order_rate_constant"/>
<variable name="MPF" public_interface="in" units="dimensionless"/>
<variable name="Wee1" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_n9</ci>
<apply>
<times/>
<ci>kn9</ci>
<ci>MPF</ci>
<ci>Wee1</ci>
</apply>
</apply>
</math>
</component>
<component name="V_10">
<variable name="V_10" public_interface="out" units="first_order_rate_constant"/>
<variable name="k10" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_10</ci>
<ci>k10</ci>
</apply>
</math>
</component>
<component name="V_11">
<variable name="V_11" public_interface="out" units="first_order_rate_constant"/>
<variable name="k11" public_interface="in" units="first_order_rate_constant"/>
<variable name="p53" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_11</ci>
<apply>
<times/>
<ci>k11</ci>
<ci>p53</ci>
</apply>
</apply>
</math>
</component>
<component name="V_12">
<variable name="V_12" public_interface="out" units="first_order_rate_constant"/>
<variable name="k12" public_interface="in" units="first_order_rate_constant"/>
<variable name="protein1433" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_12</ci>
<apply>
<times/>
<ci>k12</ci>
<ci>protein1433</ci>
</apply>
</apply>
</math>
</component>
<component name="V_13">
<variable name="V_13" public_interface="out" units="first_order_rate_constant"/>
<variable name="k13" public_interface="in" units="first_order_rate_constant"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_13</ci>
<ci>k13</ci>
</apply>
</math>
</component>
<component name="V_14">
<variable name="V_14" public_interface="out" units="first_order_rate_constant"/>
<variable name="k14" public_interface="in" units="first_order_rate_constant"/>
<variable name="k14_" public_interface="in" units="first_order_rate_constant"/>
<variable name="p53" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>V_14</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>k14</ci>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="first_order_rate_constant">1</cn>