Rendering of the source text

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<!--  FILE :hatzimanikatis_model_1999.xml

CREATED :  17th October 2002

LAST MODIFIED : 9th April 2003

AUTHOR :  Catherine Lloyd
          Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.

DESCRIPTION :  This file contains a CellML description of Hatzimanikatis, Lee and Bailey's 1999 model of the G1-S transition of the mammalian cell cycle.

CHANGES:  
  09/04/2003 - AAC - Added publication date information.  

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<article>
  <articleinfo>
  <title>Regulation of the G1-S Transition of the Mammalian Cell Cycle</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 model has been recoded to remove the reaction element.  The model opens in PCEnv and COR but unfortunately it does not run due to there being 'circular arguments' (COR) or the model being 'under-constrained' (PCEnv).  At the moment this is a limitation of the simulation software because it is unable to process nonlinear
algebraic equations that must be solved iteratively at each time step.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
In order to better understand developmental and tumour biology, extensive research on the control of the mammalian cell cycle is being carried out.  At the protein level, several molecules play a role in the control of the G1-S transition of the cell cycle.  Specifically, G1 cyclins such as cyclin E are known to form phosphorylated complexes with cyclin dependent kinases (cdk's, such as cdk2).  These complexes, which can be inhibited by other proteins, can phosphorylate pocket proteins such as pRb.  Hyperphosphorylation of pRb occurs at the time of E2F-1 release.  This transcription factor initiates the transcription of genes involved in S phase activities, including DNA polymerase. </para>

<para>
Hatzimanikatis, Lee and Bailey capture the components and interactions of cyclin E, cdk2, pRb, inhibitor and E2F-1 during the G1-S transition of the cell cycle in their mathematical model (see the figure below).    
</para>

<para>
The complete original paper reference is cited below:
</para>

<para>
<ulink url="http://www3.interscience.wiley.com/cgi-bin/abstract/71003582/START">A Mathematical Description of Regulation of the G1-S Transition of the Mammalian Cell Cycle</ulink>, V. Hatzimanikatis, K. H. Lee and J. E. Bailey, 1999, <ulink url="http://www3.interscience.wiley.com/cgi-bin/jtoc?Type=DD&amp;ID=71003582">
            <emphasis>Biotechnology and Bioengineering</emphasis>
          </ulink>, 65, 631-637.  (A <ulink url="http://www3.interscience.wiley.com/cgi-bin/fulltext?ID=71003582&amp;PLACEBO=IE.pdf">PDF</ulink> version of the article is available for Journal Members on the Biotechnology and Bioengineering website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=10550769&amp;dopt=Abstract">PubMed ID: 10550769</ulink>
</para>

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<caption>A schematic diagram of the reactions involved during the G1-S transition of the mammalian cell cycle.</caption>
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</sect1>
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        Hatzimanikatis, Lee and Bailey's 1999 model of the G1-S transition of 
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    <dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
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    <vCard:Given>K</vCard:Given>
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    <dcterms:W3CDTF>1999-12-20</dcterms:W3CDTF>
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