Location: Goldbeter, 1991 @ 930898d5d5f4 / goldbeter_annotated_1991.cellml

Author:
Dougal Cowan <devnull@localhost>
Date:
2011-05-13 09:30:07+12:00
Desc:
relativized the imports in the 1.1 version model is underconstrained
Permanent Source URI:
https://staging.physiomeproject.org/workspace/goldbeter_1991/rawfile/930898d5d5f4820b8d29b3b9572ab49f85a5873b/goldbeter_annotated_1991.cellml

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    <article>
      <articleinfo>
        <title>A Minimal Cascade Model for the Mitotic Oscillator Involving Cyclin and cdc2 Kinase</title>
        <author>
          <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
          <affiliation>
            <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
          </affiliation>
        </author>
      </articleinfo>
      <section id="sec_status">
        <title>Model Status</title>
        <para>
            The CellML model runs in OpenCell to reproduce figure 3 of the published paper. The model also runs in COR but doe to the long duration of the simulation (100 minutes) COR is not reall suitable for such a simulation. The units have been checked and they are consistent. Please note that this particular version of the CellML model has been annotated using MIRIAM URIs. These annotations were based on the <ulink url="http://www.ebi.ac.uk/biomodels-main/BIOMD0000000003">SBML version</ulink> of this model in the BioModels Database.
          </para>
      </section>
      <sect1 id="sec_structure">
        <title>Model Structure</title>
        <para>
ABSTRACT: A minimal model for the mitotic oscillator is presented. The model, built on recent experimental advances, is based on the cascade of post-translational modification that modulates the activity of cdc2 kinase during the cell cycle. The model pertains to the situation encountered in early amphibian embryos, where the accumulation of cyclin suffices to trigger the onset of mitosis. In the first cycle of the bicyclic cascade model, cyclin promotes the activation of cdc2 kinase through reversible dephosphorylation, and in the second cycle, cdc2 kinase activates a cyclin protease by reversible phosphorylation. That cyclin activates cdc2 kinase while the kinase triggers the degradation of cyclin has suggested that oscillations may originate from such a negative feedback loop [Felix, M. A., Labbe, J. C., Doree, M., Hunt, T. and Karsenti, E. (1990) Nature (London) 346, 379-382]. This conjecture is corroborated by the model, which indicates that sustained oscillations of the limit cycle type can arise in the cascade, provided that a threshold exists in the activation of cdc2 kinase by cyclin and in the activation of cyclin proteolysis by cdc2 kinase. The analysis shows how miototic oscillations may readily arise from time lags associated with these thresholds and from the delayed negative feedback provided by cdc2-induced cyclin degradation. A mechanism for the origin of the thresholds is proposed in terms of the phenomenon of zero-order ultrasensitivity previously described for biochemical systems regulated by covalent modification.
</para>
        
        <para>
The original paper reference is cited below:
</para>
        <para>
          A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase, Albert Goldbeter, 1991, <emphasis>Proceedings of the National Academy of Sciences</emphasis>, 88, 9107-9111. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/1833774">PubMed ID: 1833774</ulink>
        </para>
        
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              <objectinfo>
                <title>cell diagram</title>
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          <caption>Minimal cascade model for the mitotic oscillations between cyclin and cdc2 kinase (M) during the cell cycle.  X represents the fraction of active (phosphorylated) cyclin protease.  * represents the fraction of inactive enzymes.</caption>
        </informalfigure>
      </sect1>
    </article>
  </documentation>

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    </rdf:RDF> 
    </variable>
	
    <variable units="first_order_rate_constant" public_interface="out" name="V2" cmeta:id="V2_" initial_value="1.5">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
      <rdf:Description rdf:about="#V2_">
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	<variable units="first_order_rate_constant" public_interface="out" name="V3" cmeta:id="V3_">
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    <variable units="first_order_rate_constant" public_interface="out" name="V4" cmeta:id="V4_" initial_value="0.5">
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    <variable units="first_order_rate_constant" public_interface="out" name="VM1" cmeta:id="VM1_" initial_value="3">
	<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
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    <variable units="first_order_rate_constant" public_interface="out" name="VM3" cmeta:id="VM3_" initial_value="1">
	<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
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        <bqbiol:isVersionOf>
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	<variable units="micromolar" public_interface="in" name="C"/>
    <variable units="dimensionless" public_interface="in" name="M"/>
    
	<math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq/>
        <ci>V1</ci>
        <apply>
          <divide/>
          <apply>
            <times/>
            <ci>VM1</ci>
            <ci>C</ci>
          </apply>
          <apply>
            <plus/>
            <ci>Kc</ci>
            <ci>C</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq/>
        <ci>V3</ci>
        <apply>
          <times/>
          <ci>M</ci>
          <ci>VM3</ci>
        </apply>
      </apply>
    </math>
  </component>
  
  <connection>
    <map_components component_2="C" component_1="environment"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  <connection>
    <map_components component_2="M" component_1="environment"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  <connection>
    <map_components component_2="X" component_1="environment"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  <connection>
    <map_components component_2="M" component_1="M_star"/>
    <map_variables variable_2="M" variable_1="M"/>
	<map_variables variable_2="M_star" variable_1="M_star"/>
  </connection>
  <connection>
    <map_components component_2="X" component_1="X_star"/>
    <map_variables variable_2="X" variable_1="X"/>
	<map_variables variable_2="X_star" variable_1="X_star"/>
  </connection>
  <connection>
    <map_components component_2="model_parameters" component_1="C"/>
    <map_variables variable_2="kd" variable_1="kd"/>
    <map_variables variable_2="Kd" variable_1="Kd"/>
    <map_variables variable_2="vi" variable_1="vi"/>
    <map_variables variable_2="vd" variable_1="vd"/>
    <map_variables variable_2="C" variable_1="C"/>
  </connection>
  <connection>
    <map_components component_2="X" component_1="C"/>
    <map_variables variable_2="X" variable_1="X"/>
  </connection>
  <connection>
    <map_components component_2="model_parameters" component_1="M"/>
    <map_variables variable_2="V1" variable_1="V1"/>
    <map_variables variable_2="V2" variable_1="V2"/>
    <map_variables variable_2="K1" variable_1="K1"/>
    <map_variables variable_2="K2" variable_1="K2"/>
    <map_variables variable_2="M" variable_1="M"/>
  </connection>
  <connection>
    <map_components component_2="model_parameters" component_1="X"/>
    <map_variables variable_2="V3" variable_1="V3"/>
    <map_variables variable_2="V4" variable_1="V4"/>
    <map_variables variable_2="K3" variable_1="K3"/>
    <map_variables variable_2="K4" variable_1="K4"/>
  </connection>


<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
    
    <rdf:Description rdf:about="">
      <dc:title>A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase (Model with MIRIAM annotations)</dc:title>
      <dc:creator rdf:parseType="Resource">
        <vCard:N rdf:parseType="Resource">
          <vCard:Family>Lloyd</vCard:Family>
          <vCard:Given>Catherine</vCard:Given>
          <vCard:Other>May</vCard:Other>
        </vCard:N>
        <vCard:EMAIL rdf:parseType="Resource">
          <rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
          <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
        </vCard:EMAIL>
        <vCard:ORG rdf:parseType="Resource">
          <vCard:Orgname>The University of Auckland</vCard:Orgname>
          <vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit>
        </vCard:ORG>
      </dc:creator>
    </rdf:Description>
    
    <rdf:Description rdf:about="#goldbeter_1991">
      <bqs:reference rdf:parseType="Resource">
        <dc:subject rdf:parseType="Resource">
          <bqs:subject_type>keyword</bqs:subject_type>
          <rdf:value>
            <rdf:Bag>
              <rdf:li>oscillator</rdf:li>
              <rdf:li>cell cycle</rdf:li>
              <rdf:li>cyclin</rdf:li>
			  <rdf:li>kinase</rdf:li>
            </rdf:Bag>
          </rdf:value>
        </dc:subject>
      </bqs:reference>

      <bqs:reference rdf:parseType="Resource">
        <bqs:Pubmed_id>1833774</bqs:Pubmed_id>
        <bqs:JournalArticle rdf:parseType="Resource">
          <dc:creator>
            <rdf:Seq>
              <rdf:li rdf:parseType="Resource">
                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Goldbeter</vCard:Family>
                    <vCard:Given>A</vCard:Given>
			      </vCard:N>
                </bqs:Person>
              </rdf:li>
            </rdf:Seq>
          </dc:creator>
          <dc:title>
            A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase
          </dc:title>
          <dcterms:issued rdf:parseType="Resource">
            <dcterms:W3CDTF>1991-10-15</dcterms:W3CDTF>
          </dcterms:issued>
          <bqs:Journal rdf:parseType="Resource">
            <dc:title>Proceedings of the National Academy of Sciences USA</dc:title>
          </bqs:Journal>
		  <bqs:volume>88</bqs:volume>
          <bqs:first_page>9107</bqs:first_page>
          <bqs:last_page>9111</bqs:last_page>
        </bqs:JournalArticle>
      </bqs:reference>
	  
	  <bqmodel:isDescribedBy>
         <rdf:Bag>
           <rdf:li rdf:resource="urn:miriam:pubmed:1833774"/>
         </rdf:Bag>
       </bqmodel:isDescribedBy>
       <bqbiol:isHomologTo>
         <rdf:Bag>
           <rdf:li rdf:resource="urn:miriam:reactome:REACT_152"/>
         </rdf:Bag>
       </bqbiol:isHomologTo>
       <bqbiol:isVersionOf>
         <rdf:Bag>
           <rdf:li rdf:resource="urn:miriam:kegg.pathway:hsa04110"/>
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       </bqbiol:isVersionOf>
       <bqbiol:is>
         <rdf:Bag>
           <rdf:li rdf:resource="urn:miriam:taxonomy:8292"/>
         </rdf:Bag>
       </bqbiol:is>
    </rdf:Description>
  </rdf:RDF>
</model>