- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2008-12-15 22:37:36+13:00
- Desc:
- committing version02 of ciliberto_petrus_tyson_sible_2003
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/36d/rawfile/0341c775a921ecc74b47ebcd8298e669d72ebe9a/ciliberto_petrus_tyson_sible_2003.cellml
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<!--
This CellML file was generated on 16/12/2008 at 9:19:52 at a.m. using:
COR (0.9.31.1125)
Copyright 2002-2008 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.CellML.org/
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Kinetic Model of the Cyclin E/Cdk2 Developmental Timer in Xenopus laevis embryos</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</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 model has been checked in PCEnv and the model runs to replicate the results in the original published paper. This models uses the initial conditions that recreate the results in figure 6. The model runs in COR but the duration of the model is too long for the results to be properly displayed in COR. The units have been checked and are consistent.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The cell cycle in <emphasis>Xenopus</emphasis> embryos has been the subject of several experimental and theoretical studies. Following fertilisation, the egg and sperm nuclei undergo DNA replication, nuclear fusion and the first mitotic cellular division. The next 11 embryonic cell cycles are rapid, synchronous oscillations between DNA replication and mitosis, lacking the usual intervening gap phases, cell growth and cell cycle checkpoints. After the 12th division, the <emphasis>Xenopus</emphasis> embryo undergoes the midblastula transition (MBT), when cells become motile, embryonic transcription begins and the cell cycle acquires the gap phases and checkpoints of a typical somatic cell.
</para>
<para>
The mechanisms underlying this cell cycle remodelling are not well understood, but it is thought that they may depend in part on a maternal developmental timer driven by oscillations in the activity of cyclin E/Cdk2. Cdk2 activity oscillates twice per cell cycle, despite a constant level of its partner cyclin E. Cyclin E breaks down at a fixed time after fertilisation, usually around MBT. In an effort to better understand the mechanisms underlying these phenomena, Ciliberto <emphasis>et al.</emphasis> have developed a mathematical model of the cyclin E/Cdk2 developmental timer that describes both the oscillations in Cdk2 activity and the sudden degradation of Cyclin E when the MBT begins (see <xref linkend="fig_reaction_diagram"/> below). In this mathematical model,
<itemizedlist>
<listitem>
<para>oscillations in Cdk2 activity depend on changes in phosphorylation;</para>
</listitem>
<listitem>
<para>Cdk2 participates in a negative feedback loop with inhibitory kinase Wee1;</para>
</listitem>
<listitem>
<para>cyclin E is cooperatively removed from the oscillatory system; and</para>
</listitem>
<listitem>
<para>removed cyclin E is degraded by a pathway activated by cyclin E/Cdk2 itself.</para>
</listitem>
</itemizedlist>
</para>
<para>
The model has been described here in CellML (the raw CellML description of the Ciliberto <emphasis>et al.</emphasis> 2003 model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TFB-48V891M-3&_user=140507&_coverDate=07%2F01%2F2003&_alid=133391549&_rdoc=1&_fmt=summary&_orig=search&_qd=1&_cdi=5222&_sort=d&_docanchor=&view=c&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=ac3ac20d5deb272fb6e0b0156660bbc7">A kinetic model of the cyclin E/Cdk2 developmental timer in <emphasis>Xenopus laevis</emphasis> embryos</ulink>, Andrea Ciliberto, Matthew J. Petrus, John J. Tyson, and Jill C. Sible, 2003, <ulink url="http://www.sciencedirect.com/science?_ob=JournalURL&_cdi=5222&_auth=y&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=7d06a1ef3b4293bc0633b8269aa54192">
<emphasis>Biophysical Chemistry</emphasis>
</ulink>, 104, 573-589. (<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TFB-48V891M-3&_coverDate=07%2F01%2F2003&_alid=133391549&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5222&_sort=d&view=c&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=8b3236650c4054e9e644ebbf4cd680e0">Full text (HTML)</ulink> and PDF versions of the article are available on the <emphasis>Biophysical Chemistry</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12914904&dopt=Abstract">PubMed ID: 12914904</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram</title>
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<imagedata fileref="ciliberto_2003.png"/>
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<caption>A theoretical molecular mechanism of the cyclin E/Cdk2 developmental timer was used to construct the mathematical model. The dashed box represents a mechanism for removing cyclin E/Cdk2 from the oscillatory subsystem, which is activated by the "removed" form of cyclin E/Cdk2. The removal step is cooperative in that the more cyclin E/Cdk2 there is bound to the dashed box, the faster is the association reaction. A kinase (Kin) is introduced between cyclin E/Cdk2 and Wee1 to create a time lag in the negative feedback loop.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<ci>Xic_Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kwee</ci>
<ci>Wee1_a</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xic_PCdk2_CycE">
<variable units="dimensionless" public_interface="out" name="Xic_PCdk2_CycE" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="kwee"/>
<variable units="first_order_rate_constant" public_interface="in" name="kon"/>
<variable units="first_order_rate_constant" public_interface="in" name="k25A"/>
<variable units="first_order_rate_constant" public_interface="in" name="koff"/>
<variable units="first_order_rate_constant" public_interface="in" name="kassoc"/>
<variable units="first_order_rate_constant" public_interface="in" name="kdissoc"/>
<variable units="dimensionless" public_interface="in" name="phi"/>
<variable units="dimensionless" public_interface="in" name="Xic"/>
<variable units="dimensionless" public_interface="in" name="PCdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="Wee1_a"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic_PCdk2_CycE</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kwee</ci>
<ci>Wee1_a</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>k25A</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xic_Cdk2_CycErem">
<variable units="dimensionless" public_interface="out" name="Xic_Cdk2_CycErem" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="kedeg"/>
<variable units="first_order_rate_constant" public_interface="in" name="kon"/>
<variable units="first_order_rate_constant" public_interface="in" name="kxdeg"/>
<variable units="first_order_rate_constant" public_interface="in" name="koff"/>
<variable units="first_order_rate_constant" public_interface="in" name="kassoc"/>
<variable units="first_order_rate_constant" public_interface="in" name="kdissoc"/>
<variable units="dimensionless" public_interface="in" name="phi"/>
<variable units="dimensionless" public_interface="in" name="Deg_a"/>
<variable units="dimensionless" public_interface="in" name="Xic"/>
<variable units="dimensionless" public_interface="in" name="Cdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycE"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xic_PCdk2_CycErem">
<variable units="dimensionless" public_interface="out" name="Xic_PCdk2_CycErem" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="kedeg"/>
<variable units="first_order_rate_constant" public_interface="in" name="kon"/>
<variable units="first_order_rate_constant" public_interface="in" name="kxdeg"/>
<variable units="first_order_rate_constant" public_interface="in" name="koff"/>
<variable units="first_order_rate_constant" public_interface="in" name="kassoc"/>
<variable units="first_order_rate_constant" public_interface="in" name="kdissoc"/>
<variable units="dimensionless" public_interface="in" name="phi"/>
<variable units="dimensionless" public_interface="in" name="Deg"/>
<variable units="dimensionless" public_interface="in" name="Xic"/>
<variable units="dimensionless" public_interface="in" name="PCdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycE"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xicrem">
<variable units="dimensionless" public_interface="out" name="Xicrem" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="kedeg"/>
<variable units="first_order_rate_constant" public_interface="in" name="kxdeg"/>
<variable units="dimensionless" public_interface="in" name="Deg_a"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycErem"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xicrem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xicrem</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Cyc_total">
<variable units="dimensionless" public_interface="out" name="Cyc_total"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="Cdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="PCdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="Cdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="PCdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycErem"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Cyc_total</ci>
<apply>
<plus/>
<ci>Xic_PCdk2_CycE</ci>
<ci>Xic_Cdk2_CycE</ci>
<ci>Xic_PCdk2_CycErem</ci>
<ci>Xic_Cdk2_CycErem</ci>
<ci>PCdk2_CycErem</ci>
<ci>Cdk2_CycErem</ci>
<ci>Cdk2_CycE</ci>
<ci>PCdk2_CycE</ci>
</apply>
</apply>
</math>
</component>
<component name="Xic_total">
<variable units="dimensionless" public_interface="out" name="Xic_total"/>
<variable units="dimensionless" public_interface="in" name="Xic"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycE"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xicrem"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Xic_total</ci>
<apply>
<divide/>
<apply>
<plus/>
<ci>Xic</ci>
<ci>Xic_PCdk2_CycE</ci>
<ci>Xic_Cdk2_CycE</ci>
<ci>Xic_PCdk2_CycErem</ci>
<ci>Xic_Cdk2_CycErem</ci>
<ci>Xicrem</ci>
</apply>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
</math>
</component>
<component name="kinetic_parameters">
<variable units="first_order_rate_constant" public_interface="out" name="kwee" initial_value="1.5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k25A" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="kon" initial_value="0.02"/>
<variable units="first_order_rate_constant" public_interface="out" name="koff" initial_value="0.0001"/>
<variable units="first_order_rate_constant" public_interface="out" name="kassoc" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="kdissoc" initial_value="0.001"/>
<variable units="first_order_rate_constant" public_interface="out" name="kedeg" initial_value="0.017"/>
<variable units="first_order_rate_constant" public_interface="out" name="kxdeg" initial_value="0.01"/>
<variable units="dimensionless" public_interface="out" name="phi"/>
<variable units="dimensionless" public_interface="out" name="Deg" initial_value="0"/>
<variable units="dimensionless" name="epsilon" initial_value="0.001"/>
<variable units="dimensionless" public_interface="out" name="pool"/>
<variable units="dimensionless" name="n" initial_value="4"/>
<variable units="dimensionless" name="L" initial_value="0.4"/>
<variable units="dimensionless" public_interface="in" name="Cdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="PCdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_Cdk2_CycErem"/>
<variable units="dimensionless" public_interface="in" name="Xic_PCdk2_CycErem"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>phi</ci>
<apply>
<divide/>
<apply>
<plus/>
<ci>epsilon</ci>
<apply>
<power/>
<ci>pool</ci>
<ci>n</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>L</ci>
<ci>n</ci>
</apply>
<apply>
<power/>
<ci>pool</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>pool</ci>
<apply>
<plus/>
<ci>Cdk2_CycErem</ci>
<ci>PCdk2_CycErem</ci>
<ci>Xic_Cdk2_CycErem</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="Cdk2_CycE"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="PCdk2_CycE"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Wee1_a"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Kin_a"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Cdk2_CycErem"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="PCdk2_CycErem"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Deg_a"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Xic"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Xic_total"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Xic_Cdk2_CycE"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Xic_PCdk2_CycE"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Xic_Cdk2_CycErem"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Xic_PCdk2_CycErem"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Xicrem"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Cyc_total"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="Wee1_a" component_1="Cdk2_CycE"/>
<map_variables variable_2="Wee1_a" variable_1="Wee1_a"/>
</connection>
<connection>
<map_components component_2="PCdk2_CycE" component_1="Cdk2_CycE"/>
<map_variables variable_2="PCdk2_CycE" variable_1="PCdk2_CycE"/>
<map_variables variable_2="Cdk2_CycE" variable_1="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Cdk2_CycErem" component_1="Cdk2_CycE"/>
<map_variables variable_2="Cdk2_CycErem" variable_1="Cdk2_CycErem"/>
<map_variables variable_2="Cdk2_CycE" variable_1="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic" component_1="Cdk2_CycE"/>
<map_variables variable_2="Xic" variable_1="Xic"/>
<map_variables variable_2="Cdk2_CycE" variable_1="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic_Cdk2_CycE" component_1="Cdk2_CycE"/>
<map_variables variable_2="Xic_Cdk2_CycE" variable_1="Xic_Cdk2_CycE"/>
<map_variables variable_2="Cdk2_CycE" variable_1="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Wee1_a" component_1="PCdk2_CycE"/>
<map_variables variable_2="Wee1_a" variable_1="Wee1_a"/>
</connection>
<connection>
<map_components component_2="PCdk2_CycErem" component_1="PCdk2_CycE"/>
<map_variables variable_2="PCdk2_CycErem" variable_1="PCdk2_CycErem"/>
<map_variables variable_2="PCdk2_CycE" variable_1="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic" component_1="PCdk2_CycE"/>
<map_variables variable_2="Xic" variable_1="Xic"/>
<map_variables variable_2="PCdk2_CycE" variable_1="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic_PCdk2_CycE" component_1="PCdk2_CycE"/>
<map_variables variable_2="Xic_PCdk2_CycE" variable_1="Xic_PCdk2_CycE"/>
<map_variables variable_2="PCdk2_CycE" variable_1="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Cdk2_CycE" component_1="Kin_a"/>
<map_variables variable_2="Cdk2_CycE" variable_1="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic" component_1="Cdk2_CycErem"/>
<map_variables variable_2="Xic" variable_1="Xic"/>
<map_variables variable_2="Cdk2_CycErem" variable_1="Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Xic_Cdk2_CycErem" component_1="Cdk2_CycErem"/>
<map_variables variable_2="Xic_Cdk2_CycErem" variable_1="Xic_Cdk2_CycErem"/>
<map_variables variable_2="Cdk2_CycErem" variable_1="Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Xic" component_1="PCdk2_CycErem"/>
<map_variables variable_2="Xic" variable_1="Xic"/>
<map_variables variable_2="PCdk2_CycErem" variable_1="PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Deg_a" component_1="PCdk2_CycErem"/>
<map_variables variable_2="Deg_a" variable_1="Deg_a"/>
</connection>
<connection>
<map_components component_2="Xic_PCdk2_CycErem" component_1="PCdk2_CycErem"/>
<map_variables variable_2="Xic_PCdk2_CycErem" variable_1="Xic_PCdk2_CycErem"/>
<map_variables variable_2="PCdk2_CycErem" variable_1="PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Kin_a" component_1="Wee1_a"/>
<map_variables variable_2="Kin_a" variable_1="Kin_a"/>
</connection>
<connection>
<map_components component_2="Cdk2_CycErem" component_1="Deg_a"/>
<map_variables variable_2="Cdk2_CycErem" variable_1="Cdk2_CycErem"/>
<map_variables variable_2="Deg_a" variable_1="Deg_a"/>
</connection>
<connection>
<map_components component_2="Xic_Cdk2_CycE" component_1="Xic"/>
<map_variables variable_2="Xic_Cdk2_CycE" variable_1="Xic_Cdk2_CycE"/>
<map_variables variable_2="Xic" variable_1="Xic"/>
</connection>
<connection>
<map_components component_2="Xic_PCdk2_CycE" component_1="Xic"/>
<map_variables variable_2="Xic_PCdk2_CycE" variable_1="Xic_PCdk2_CycE"/>
<map_variables variable_2="Xic" variable_1="Xic"/>
</connection>
<connection>
<map_components component_2="Xic_PCdk2_CycE" component_1="Cyc_total"/>
<map_variables variable_2="Xic_PCdk2_CycE" variable_1="Xic_PCdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic_Cdk2_CycE" component_1="Cyc_total"/>
<map_variables variable_2="Xic_Cdk2_CycE" variable_1="Xic_Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Cdk2_CycE" component_1="Cyc_total"/>
<map_variables variable_2="Cdk2_CycE" variable_1="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="PCdk2_CycE" component_1="Cyc_total"/>
<map_variables variable_2="PCdk2_CycE" variable_1="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Cdk2_CycErem" component_1="Cyc_total"/>
<map_variables variable_2="Cdk2_CycErem" variable_1="Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="PCdk2_CycErem" component_1="Cyc_total"/>
<map_variables variable_2="PCdk2_CycErem" variable_1="PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Xic_PCdk2_CycErem" component_1="Cyc_total"/>
<map_variables variable_2="Xic_PCdk2_CycErem" variable_1="Xic_PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Xic_Cdk2_CycErem" component_1="Cyc_total"/>
<map_variables variable_2="Xic_Cdk2_CycErem" variable_1="Xic_Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Xic" component_1="Xic_total"/>
<map_variables variable_2="Xic" variable_1="Xic"/>
</connection>
<connection>
<map_components component_2="Xic_Cdk2_CycErem" component_1="Xic_total"/>
<map_variables variable_2="Xic_Cdk2_CycErem" variable_1="Xic_Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Xic_PCdk2_CycE" component_1="Xic_total"/>
<map_variables variable_2="Xic_PCdk2_CycE" variable_1="Xic_PCdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic_Cdk2_CycE" component_1="Xic_total"/>
<map_variables variable_2="Xic_Cdk2_CycE" variable_1="Xic_Cdk2_CycE"/>
</connection>
<connection>
<map_components component_2="Xic_PCdk2_CycErem" component_1="Xic_total"/>
<map_variables variable_2="Xic_PCdk2_CycErem" variable_1="Xic_PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_2="Xicrem" component_1="Xic_total"/>
<map_variables variable_2="Xicrem" variable_1="Xicrem"/>
</connection>
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Ciliberto et al.'s 2003 kinetic model of the cyclin E/Cdk2 developmental timer in Xenopus laevis embryos.
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