Proteomic Shifts in Embryonic Stem Cells with Gene Dose Modifications Suggest the Presence of Balancer Proteins in Protein Regulatory Networks
Identifieur interne : 000792 ( Ncbi/Merge ); précédent : 000791; suivant : 000793Proteomic Shifts in Embryonic Stem Cells with Gene Dose Modifications Suggest the Presence of Balancer Proteins in Protein Regulatory Networks
Auteurs : Lei Mao [Allemagne] ; Claus Zabel [Allemagne] ; Marion Herrmann [Allemagne] ; Tobias Nolden [Allemagne] ; Florian Mertes [Allemagne] ; Laetitia Magnol [France] ; Caroline Chabert [France] ; Daniela Hartl [Allemagne] ; Yann Herault [France] ; Jean Maurice Delabar [France] ; Thomas Manke [Allemagne] ; Heinz Himmelbauer [Allemagne] ; Joachim Klose [Allemagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2007.
Abstract
Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual genes or displayed aneuploidy over a genomic region encompassing 14 genes. The number of variant proteins detected per cell line ranged between 70 and 110, and did not correlate with the number of modified genes. In cell lines with single gene mutations, up and down-regulated proteins were always in balance in comparison to parental cell lines regarding number as well as concentration of differentially expressed proteins. In contrast, dose alteration of 14 genes resulted in an unequal number of up and down-regulated proteins, though the balance was kept at the level of protein concentration. We propose that the observed protein changes might partially be explained by a proteomic network response. Hence, we hypothesize the existence of a class of “balancer” proteins within the proteomic network, defined as proteins that buffer or cushion a system, and thus oppose multiple system disturbances. Through database queries and resilience analysis of the protein interaction network, we found that potential balancer proteins are of high cellular abundance, possess a low number of direct interaction partners, and show great allelic variation. Moreover, balancer proteins contribute more heavily to the network entropy, and thus are of high importance in terms of system resilience. We propose that the “elasticity” of the proteomic regulatory network mediated by balancer proteins may compensate for changes that occur under diseased conditions.
Url:
DOI: 10.1371/journal.pone.0001218
PubMed: 18043732
PubMed Central: 2077926
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<front><div type="abstract" xml:lang="en"><p>Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual genes or displayed aneuploidy over a genomic region encompassing 14 genes. The number of variant proteins detected per cell line ranged between 70 and 110, and did not correlate with the number of modified genes. In cell lines with single gene mutations, up and down-regulated proteins were always in balance in comparison to parental cell lines regarding number as well as concentration of differentially expressed proteins. In contrast, dose alteration of 14 genes resulted in an unequal number of up and down-regulated proteins, though the balance was kept at the level of protein concentration. We propose that the observed protein changes might partially be explained by a proteomic network response. Hence, we hypothesize the existence of a class of “balancer” proteins within the proteomic network, defined as proteins that buffer or cushion a system, and thus oppose multiple system disturbances. Through database queries and resilience analysis of the protein interaction network, we found that potential balancer proteins are of high cellular abundance, possess a low number of direct interaction partners, and show great allelic variation. Moreover, balancer proteins contribute more heavily to the network entropy, and thus are of high importance in terms of system resilience. We propose that the “elasticity” of the proteomic regulatory network mediated by balancer proteins may compensate for changes that occur under diseased conditions.</p>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title>PLoS ONE</journal-title>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18043732</article-id>
<article-id pub-id-type="pmc">2077926</article-id>
<article-id pub-id-type="publisher-id">07-PONE-RA-01635R1</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0001218</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline"><subject>Cell Biology/Gene Expression</subject>
<subject>Computational Biology/Systems Biology</subject>
<subject>Mental Health/Alzheimer Disease</subject>
</subj-group>
</article-categories>
<title-group><article-title>Proteomic Shifts in Embryonic Stem Cells with Gene Dose Modifications Suggest the Presence of Balancer Proteins in Protein Regulatory Networks</article-title>
<alt-title alt-title-type="running-head">Balancing Proteomic Networks</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Mao</surname>
<given-names>Lei</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zabel</surname>
<given-names>Claus</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Herrmann</surname>
<given-names>Marion</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nolden</surname>
<given-names>Tobias</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mertes</surname>
<given-names>Florian</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Magnol</surname>
<given-names>Laetitia</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chabert</surname>
<given-names>Caroline</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hartl</surname>
<given-names>Daniela</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Herault</surname>
<given-names>Yann</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Delabar</surname>
<given-names>Jean Maurice</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Manke</surname>
<given-names>Thomas</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Himmelbauer</surname>
<given-names>Heinz</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Klose</surname>
<given-names>Joachim</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Institute for Human Genetics, Charité-University Medicine Berlin, Germany</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Max Planck Institute for Molecular Genetics, Berlin, Germany</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Institut de Transgénose, IEM, UMR6218, CNRS Uni Orléans, Orléans, France</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>EA 3508, Université Paris Diderot-Paris 7, Paris, France</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Huang</surname>
<given-names>Sui</given-names>
</name>
<role>Academic Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Children's Hospital Boston, United States of America</aff>
<author-notes><corresp id="cor1">* To whom correspondence should be addressed. E-mail: <email>lei.mao@charite.de</email>
</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: LM CZ JK. Performed the experiments: LM MH TN FM. Analyzed the data: TM LM DH. Contributed reagents/materials/analysis tools: JD LM CC YH. Wrote the paper: TM LM HH JK.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2007</year>
</pub-date>
<pub-date pub-type="epub"><day>28</day>
<month>11</month>
<year>2007</year>
</pub-date>
<volume>2</volume>
<issue>11</issue>
<elocation-id>e1218</elocation-id>
<history><date date-type="received"><day>2</day>
<month>7</month>
<year>2007</year>
</date>
<date date-type="accepted"><day>1</day>
<month>11</month>
<year>2007</year>
</date>
</history>
<copyright-statement>Mao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
<copyright-year>2007</copyright-year>
<abstract><p>Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual genes or displayed aneuploidy over a genomic region encompassing 14 genes. The number of variant proteins detected per cell line ranged between 70 and 110, and did not correlate with the number of modified genes. In cell lines with single gene mutations, up and down-regulated proteins were always in balance in comparison to parental cell lines regarding number as well as concentration of differentially expressed proteins. In contrast, dose alteration of 14 genes resulted in an unequal number of up and down-regulated proteins, though the balance was kept at the level of protein concentration. We propose that the observed protein changes might partially be explained by a proteomic network response. Hence, we hypothesize the existence of a class of “balancer” proteins within the proteomic network, defined as proteins that buffer or cushion a system, and thus oppose multiple system disturbances. Through database queries and resilience analysis of the protein interaction network, we found that potential balancer proteins are of high cellular abundance, possess a low number of direct interaction partners, and show great allelic variation. Moreover, balancer proteins contribute more heavily to the network entropy, and thus are of high importance in terms of system resilience. We propose that the “elasticity” of the proteomic regulatory network mediated by balancer proteins may compensate for changes that occur under diseased conditions.</p>
</abstract>
<counts><page-count count="12"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>France</li>
</country>
<region><li>Berlin</li>
<li>Centre-Val de Loire</li>
<li>Région Centre</li>
<li>Île-de-France</li>
</region>
<settlement><li>Berlin</li>
<li>Orléans</li>
<li>Paris</li>
</settlement>
<orgName><li>Université Paris Diderot-Paris 7</li>
</orgName>
</list>
<tree><country name="Allemagne"><noRegion><name sortKey="Mao, Lei" sort="Mao, Lei" uniqKey="Mao L" first="Lei" last="Mao">Lei Mao</name>
</noRegion>
<name sortKey="Hartl, Daniela" sort="Hartl, Daniela" uniqKey="Hartl D" first="Daniela" last="Hartl">Daniela Hartl</name>
<name sortKey="Herrmann, Marion" sort="Herrmann, Marion" uniqKey="Herrmann M" first="Marion" last="Herrmann">Marion Herrmann</name>
<name sortKey="Himmelbauer, Heinz" sort="Himmelbauer, Heinz" uniqKey="Himmelbauer H" first="Heinz" last="Himmelbauer">Heinz Himmelbauer</name>
<name sortKey="Klose, Joachim" sort="Klose, Joachim" uniqKey="Klose J" first="Joachim" last="Klose">Joachim Klose</name>
<name sortKey="Manke, Thomas" sort="Manke, Thomas" uniqKey="Manke T" first="Thomas" last="Manke">Thomas Manke</name>
<name sortKey="Mao, Lei" sort="Mao, Lei" uniqKey="Mao L" first="Lei" last="Mao">Lei Mao</name>
<name sortKey="Mertes, Florian" sort="Mertes, Florian" uniqKey="Mertes F" first="Florian" last="Mertes">Florian Mertes</name>
<name sortKey="Nolden, Tobias" sort="Nolden, Tobias" uniqKey="Nolden T" first="Tobias" last="Nolden">Tobias Nolden</name>
<name sortKey="Zabel, Claus" sort="Zabel, Claus" uniqKey="Zabel C" first="Claus" last="Zabel">Claus Zabel</name>
</country>
<country name="France"><region name="Centre-Val de Loire"><name sortKey="Magnol, Laetitia" sort="Magnol, Laetitia" uniqKey="Magnol L" first="Laetitia" last="Magnol">Laetitia Magnol</name>
</region>
<name sortKey="Chabert, Caroline" sort="Chabert, Caroline" uniqKey="Chabert C" first="Caroline" last="Chabert">Caroline Chabert</name>
<name sortKey="Delabar, Jean Maurice" sort="Delabar, Jean Maurice" uniqKey="Delabar J" first="Jean Maurice" last="Delabar">Jean Maurice Delabar</name>
<name sortKey="Herault, Yann" sort="Herault, Yann" uniqKey="Herault Y" first="Yann" last="Herault">Yann Herault</name>
</country>
</tree>
</affiliations>
</record>
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