Mechanism of Action of Compound-13: An α1-Selective Small Molecule Activator of AMPK
Identifieur interne : 003733 ( Main/Exploration ); précédent : 003732; suivant : 003734Mechanism of Action of Compound-13: An α1-Selective Small Molecule Activator of AMPK
Auteurs : Roger W. Hunter [Royaume-Uni, Suisse] ; Marc Foretz [France] ; Laurent Bultot [Suisse] ; Morgan D. Fullerton [Canada] ; Maria Deak [Suisse] ; Fiona A. Ross [Royaume-Uni] ; Simon A. Hawley [Royaume-Uni] ; Natalia Shpiro [Royaume-Uni] ; Benoit Viollet [France] ; Denis Barron [Suisse] ; Bruce E. Kemp [Australie] ; Gregory R. Steinberg [Canada] ; D. Grahame Hardie [Royaume-Uni] ; Kei Sakamoto [Royaume-Uni, Suisse]Source :
- Chemistry & Biology [ 1074-5521 ] ; 2014.
Descripteurs français
- KwdFr :
- AMP (pharmacologie), AMP-Activated Protein Kinases (), AMP-Activated Protein Kinases (métabolisme), Acides gras (métabolisme), Activateurs d'enzymes (métabolisme), Activateurs d'enzymes (pharmacologie), Activation enzymatique (), Animaux, Bibliothèques de petites molécules (métabolisme), Bibliothèques de petites molécules (pharmacologie), Données de séquences moléculaires, Estérification (), Hépatocytes (), Hépatocytes (cytologie), Lipogenèse (), Promédicaments (métabolisme), Promédicaments (pharmacologie), Protéines recombinantes (), Protéines recombinantes (métabolisme), Souris, Sous-unités de protéines (), Sous-unités de protéines (agonistes), Sous-unités de protéines (métabolisme), Spécificité du substrat, Séquence d'acides aminés, Transduction du signal ().
- MESH :
- agonistes : Sous-unités de protéines.
- cytologie : Hépatocytes.
- métabolisme : AMP-Activated Protein Kinases, Acides gras, Activateurs d'enzymes, Bibliothèques de petites molécules, Promédicaments, Protéines recombinantes, Sous-unités de protéines.
- pharmacologie : AMP, Activateurs d'enzymes, Bibliothèques de petites molécules, Promédicaments.
- AMP-Activated Protein Kinases, Activation enzymatique, Animaux, Données de séquences moléculaires, Estérification, Hépatocytes, Lipogenèse, Protéines recombinantes, Souris, Sous-unités de protéines, Spécificité du substrat, Séquence d'acides aminés, Transduction du signal.
English descriptors
- KwdEn :
- AMP-Activated Protein Kinases (chemistry), AMP-Activated Protein Kinases (metabolism), Adenosine Monophosphate (pharmacology), Amino Acid Sequence, Animals, Enzyme Activation (drug effects), Enzyme Activators (metabolism), Enzyme Activators (pharmacology), Esterification (drug effects), Fatty Acids (metabolism), Hepatocytes (cytology), Hepatocytes (drug effects), Lipogenesis (drug effects), Mice, Molecular Sequence Data, Prodrugs (metabolism), Prodrugs (pharmacology), Protein Subunits (agonists), Protein Subunits (chemistry), Protein Subunits (metabolism), Recombinant Proteins (chemistry), Recombinant Proteins (metabolism), Signal Transduction (drug effects), Small Molecule Libraries (metabolism), Small Molecule Libraries (pharmacology), Substrate Specificity.
- MESH :
- chemical , agonists : Protein Subunits.
- chemical , chemistry : AMP-Activated Protein Kinases, Protein Subunits, Recombinant Proteins.
- chemical , metabolism : AMP-Activated Protein Kinases, Enzyme Activators, Fatty Acids, Prodrugs, Protein Subunits, Recombinant Proteins, Small Molecule Libraries.
- chemical , pharmacology : Adenosine Monophosphate, Enzyme Activators, Prodrugs, Small Molecule Libraries.
- cytology : Hepatocytes.
- drug effects : Enzyme Activation, Esterification, Hepatocytes, Lipogenesis, Signal Transduction.
- Amino Acid Sequence, Animals, Mice, Molecular Sequence Data, Substrate Specificity.
Abstract
AMPK is a sensor of cellular energy status and a promising target for drugs aimed at metabolic disorders. We have studied the selectivity and mechanism of a recently described activator, C2, and its cell-permeable prodrug, C13. C2 was a potent allosteric activator of α1-complexes that, like AMP, also protected against Thr172 dephosphorylation. Compared with AMP, C2 caused only partial allosteric activation of α2-complexes and failed to protect them against dephosphorylation. We show that both effects could be fully restored by exchanging part of the linker between the autoinhibitory and C-terminal domains in α2, containing the equivalent region from α1 thought to interact with AMP bound in site 3 of the γ subunit. Consistent with our results in cell-free assays, C13 potently inhibited lipid synthesis in hepatocytes from wild-type and was largely ineffective in AMPK-knockout hepatocytes; its effects were more severely affected by knockout of α1 than of α2, β1, or β2.
Url:
DOI: 10.1016/j.chembiol.2014.05.014
PubMed: 25036776
PubMed Central: 4104029
Affiliations:
- Australie, Canada, France, Royaume-Uni, Suisse
- Canton de Vaud, Ontario, Victoria (État), Île-de-France
- Hamilton (Ontario), Lausanne, Melbourne, Paris
- Université McMaster, Université Paris-Descartes, Université de Melbourne
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Le document en format XML
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<author><name sortKey="Ross, Fiona A" sort="Ross, Fiona A" uniqKey="Ross F" first="Fiona A." last="Ross">Fiona A. Ross</name>
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<country xml:lang="fr">Royaume-Uni</country>
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</affiliation>
</author>
<author><name sortKey="Hawley, Simon A" sort="Hawley, Simon A" uniqKey="Hawley S" first="Simon A." last="Hawley">Simon A. Hawley</name>
<affiliation wicri:level="1"><nlm:aff id="aff7">Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Shpiro, Natalia" sort="Shpiro, Natalia" uniqKey="Shpiro N" first="Natalia" last="Shpiro">Natalia Shpiro</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Viollet, Benoit" sort="Viollet, Benoit" uniqKey="Viollet B" first="Benoit" last="Viollet">Benoit Viollet</name>
<affiliation wicri:level="1"><nlm:aff id="aff3">Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Inserm, U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris</wicri:regionArea>
<wicri:noRegion>75014 Paris</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff4">CNRS, UMR8104, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>CNRS, UMR8104, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff5">Université Paris Descartes, Sorbonne Paris cité, 75006 Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Descartes, Sorbonne Paris cité, 75006 Paris</wicri:regionArea>
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<region type="région" nuts="2">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris-Descartes</orgName>
</affiliation>
</author>
<author><name sortKey="Barron, Denis" sort="Barron, Denis" uniqKey="Barron D" first="Denis" last="Barron">Denis Barron</name>
<affiliation wicri:level="1"><nlm:aff id="aff2">Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kemp, Bruce E" sort="Kemp, Bruce E" uniqKey="Kemp B" first="Bruce E." last="Kemp">Bruce E. Kemp</name>
<affiliation wicri:level="4"><nlm:aff id="aff8">Protein Chemistry and Metabolism, St. Vincent’s Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Protein Chemistry and Metabolism, St. Vincent’s Institute and Department of Medicine, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R." last="Steinberg">Gregory R. Steinberg</name>
<affiliation wicri:level="4"><nlm:aff id="aff6">Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main West Street, Hamilton ON L8N 3Z5</wicri:regionArea>
<orgName type="university">Université McMaster</orgName>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hardie, D Grahame" sort="Hardie, D Grahame" uniqKey="Hardie D" first="D. Grahame" last="Hardie">D. Grahame Hardie</name>
<affiliation wicri:level="1"><nlm:aff id="aff7">Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH</wicri:regionArea>
<wicri:noRegion>Dundee DD1 5EH</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sakamoto, Kei" sort="Sakamoto, Kei" uniqKey="Sakamoto K" first="Kei" last="Sakamoto">Kei Sakamoto</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland</wicri:regionArea>
<wicri:noRegion>DD1 5EH Scotland</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2">Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne, Switzerland</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Nestlé Institute of Health Sciences SA, EPFL Innovation Park, bâtiment G, 1015 Lausanne</wicri:regionArea>
<placeName><settlement type="city">Lausanne</settlement>
<region nuts="3" type="region">Canton de Vaud</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Chemistry & Biology</title>
<idno type="ISSN">1074-5521</idno>
<idno type="eISSN">1879-1301</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP-Activated Protein Kinases (chemistry)</term>
<term>AMP-Activated Protein Kinases (metabolism)</term>
<term>Adenosine Monophosphate (pharmacology)</term>
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Enzyme Activation (drug effects)</term>
<term>Enzyme Activators (metabolism)</term>
<term>Enzyme Activators (pharmacology)</term>
<term>Esterification (drug effects)</term>
<term>Fatty Acids (metabolism)</term>
<term>Hepatocytes (cytology)</term>
<term>Hepatocytes (drug effects)</term>
<term>Lipogenesis (drug effects)</term>
<term>Mice</term>
<term>Molecular Sequence Data</term>
<term>Prodrugs (metabolism)</term>
<term>Prodrugs (pharmacology)</term>
<term>Protein Subunits (agonists)</term>
<term>Protein Subunits (chemistry)</term>
<term>Protein Subunits (metabolism)</term>
<term>Recombinant Proteins (chemistry)</term>
<term>Recombinant Proteins (metabolism)</term>
<term>Signal Transduction (drug effects)</term>
<term>Small Molecule Libraries (metabolism)</term>
<term>Small Molecule Libraries (pharmacology)</term>
<term>Substrate Specificity</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>AMP (pharmacologie)</term>
<term>AMP-Activated Protein Kinases ()</term>
<term>AMP-Activated Protein Kinases (métabolisme)</term>
<term>Acides gras (métabolisme)</term>
<term>Activateurs d'enzymes (métabolisme)</term>
<term>Activateurs d'enzymes (pharmacologie)</term>
<term>Activation enzymatique ()</term>
<term>Animaux</term>
<term>Bibliothèques de petites molécules (métabolisme)</term>
<term>Bibliothèques de petites molécules (pharmacologie)</term>
<term>Données de séquences moléculaires</term>
<term>Estérification ()</term>
<term>Hépatocytes ()</term>
<term>Hépatocytes (cytologie)</term>
<term>Lipogenèse ()</term>
<term>Promédicaments (métabolisme)</term>
<term>Promédicaments (pharmacologie)</term>
<term>Protéines recombinantes ()</term>
<term>Protéines recombinantes (métabolisme)</term>
<term>Souris</term>
<term>Sous-unités de protéines ()</term>
<term>Sous-unités de protéines (agonistes)</term>
<term>Sous-unités de protéines (métabolisme)</term>
<term>Spécificité du substrat</term>
<term>Séquence d'acides aminés</term>
<term>Transduction du signal ()</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en"><term>Protein Subunits</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>AMP-Activated Protein Kinases</term>
<term>Protein Subunits</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term>
<term>Enzyme Activators</term>
<term>Fatty Acids</term>
<term>Prodrugs</term>
<term>Protein Subunits</term>
<term>Recombinant Proteins</term>
<term>Small Molecule Libraries</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine Monophosphate</term>
<term>Enzyme Activators</term>
<term>Prodrugs</term>
<term>Small Molecule Libraries</term>
</keywords>
<keywords scheme="MESH" qualifier="agonistes" xml:lang="fr"><term>Sous-unités de protéines</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Hépatocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Hepatocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Enzyme Activation</term>
<term>Esterification</term>
<term>Hepatocytes</term>
<term>Lipogenesis</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term>
<term>Acides gras</term>
<term>Activateurs d'enzymes</term>
<term>Bibliothèques de petites molécules</term>
<term>Promédicaments</term>
<term>Protéines recombinantes</term>
<term>Sous-unités de protéines</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>AMP</term>
<term>Activateurs d'enzymes</term>
<term>Bibliothèques de petites molécules</term>
<term>Promédicaments</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Mice</term>
<term>Molecular Sequence Data</term>
<term>Substrate Specificity</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>AMP-Activated Protein Kinases</term>
<term>Activation enzymatique</term>
<term>Animaux</term>
<term>Données de séquences moléculaires</term>
<term>Estérification</term>
<term>Hépatocytes</term>
<term>Lipogenèse</term>
<term>Protéines recombinantes</term>
<term>Souris</term>
<term>Sous-unités de protéines</term>
<term>Spécificité du substrat</term>
<term>Séquence d'acides aminés</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p>AMPK is a sensor of cellular energy status and a promising target for drugs aimed at metabolic disorders. We have studied the selectivity and mechanism of a recently described activator, C2, and its cell-permeable prodrug, C13. C2 was a potent allosteric activator of α1-complexes that, like AMP, also protected against Thr172 dephosphorylation. Compared with AMP, C2 caused only partial allosteric activation of α2-complexes and failed to protect them against dephosphorylation. We show that both effects could be fully restored by exchanging part of the linker between the autoinhibitory and C-terminal domains in α2, containing the equivalent region from α1 thought to interact with AMP bound in site 3 of the γ subunit. Consistent with our results in cell-free assays, C13 potently inhibited lipid synthesis in hepatocytes from wild-type and was largely ineffective in AMPK-knockout hepatocytes; its effects were more severely affected by knockout of α1 than of α2, β1, or β2.</p>
</div>
</front>
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<author><name sortKey="Salt, I" uniqKey="Salt I">I. Salt</name>
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<author><name sortKey="Scott, J" uniqKey="Scott J">J. Scott</name>
</author>
<author><name sortKey="Hardie, D G" uniqKey="Hardie D">D.G. Hardie</name>
</author>
<author><name sortKey="Carling, D" uniqKey="Carling D">D. Carling</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xiao, B" uniqKey="Xiao B">B. Xiao</name>
</author>
<author><name sortKey="Heath, R" uniqKey="Heath R">R. Heath</name>
</author>
<author><name sortKey="Saiu, P" uniqKey="Saiu P">P. Saiu</name>
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<author><name sortKey="Leone, P" uniqKey="Leone P">P. Leone</name>
</author>
<author><name sortKey="Jing, C" uniqKey="Jing C">C. Jing</name>
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<author><name sortKey="Walker, P A" uniqKey="Walker P">P.A. Walker</name>
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</author>
<author><name sortKey="Davis, C T" uniqKey="Davis C">C.T. Davis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xiao, B" uniqKey="Xiao B">B. Xiao</name>
</author>
<author><name sortKey="Sanders, M J" uniqKey="Sanders M">M.J. Sanders</name>
</author>
<author><name sortKey="Underwood, E" uniqKey="Underwood E">E. Underwood</name>
</author>
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</author>
<author><name sortKey="Mayer, F V" uniqKey="Mayer F">F.V. Mayer</name>
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<author><name sortKey="Carmena, D" uniqKey="Carmena D">D. Carmena</name>
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</author>
<author><name sortKey="Haire, L F" uniqKey="Haire L">L.F. Haire</name>
</author>
</analytic>
</biblStruct>
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</author>
<author><name sortKey="Sanders, M J" uniqKey="Sanders M">M.J. Sanders</name>
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</biblStruct>
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<author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name>
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<author><name sortKey="Wu, J W" uniqKey="Wu J">J.W. Wu</name>
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</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Canada</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>Suisse</li>
</country>
<region><li>Canton de Vaud</li>
<li>Ontario</li>
<li>Victoria (État)</li>
<li>Île-de-France</li>
</region>
<settlement><li>Hamilton (Ontario)</li>
<li>Lausanne</li>
<li>Melbourne</li>
<li>Paris</li>
</settlement>
<orgName><li>Université McMaster</li>
<li>Université Paris-Descartes</li>
<li>Université de Melbourne</li>
</orgName>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Hunter, Roger W" sort="Hunter, Roger W" uniqKey="Hunter R" first="Roger W." last="Hunter">Roger W. Hunter</name>
</noRegion>
<name sortKey="Hardie, D Grahame" sort="Hardie, D Grahame" uniqKey="Hardie D" first="D. Grahame" last="Hardie">D. Grahame Hardie</name>
<name sortKey="Hawley, Simon A" sort="Hawley, Simon A" uniqKey="Hawley S" first="Simon A." last="Hawley">Simon A. Hawley</name>
<name sortKey="Ross, Fiona A" sort="Ross, Fiona A" uniqKey="Ross F" first="Fiona A." last="Ross">Fiona A. Ross</name>
<name sortKey="Sakamoto, Kei" sort="Sakamoto, Kei" uniqKey="Sakamoto K" first="Kei" last="Sakamoto">Kei Sakamoto</name>
<name sortKey="Shpiro, Natalia" sort="Shpiro, Natalia" uniqKey="Shpiro N" first="Natalia" last="Shpiro">Natalia Shpiro</name>
</country>
<country name="Suisse"><region name="Canton de Vaud"><name sortKey="Hunter, Roger W" sort="Hunter, Roger W" uniqKey="Hunter R" first="Roger W." last="Hunter">Roger W. Hunter</name>
</region>
<name sortKey="Barron, Denis" sort="Barron, Denis" uniqKey="Barron D" first="Denis" last="Barron">Denis Barron</name>
<name sortKey="Bultot, Laurent" sort="Bultot, Laurent" uniqKey="Bultot L" first="Laurent" last="Bultot">Laurent Bultot</name>
<name sortKey="Deak, Maria" sort="Deak, Maria" uniqKey="Deak M" first="Maria" last="Deak">Maria Deak</name>
<name sortKey="Sakamoto, Kei" sort="Sakamoto, Kei" uniqKey="Sakamoto K" first="Kei" last="Sakamoto">Kei Sakamoto</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Foretz, Marc" sort="Foretz, Marc" uniqKey="Foretz M" first="Marc" last="Foretz">Marc Foretz</name>
</region>
<name sortKey="Foretz, Marc" sort="Foretz, Marc" uniqKey="Foretz M" first="Marc" last="Foretz">Marc Foretz</name>
<name sortKey="Foretz, Marc" sort="Foretz, Marc" uniqKey="Foretz M" first="Marc" last="Foretz">Marc Foretz</name>
<name sortKey="Viollet, Benoit" sort="Viollet, Benoit" uniqKey="Viollet B" first="Benoit" last="Viollet">Benoit Viollet</name>
<name sortKey="Viollet, Benoit" sort="Viollet, Benoit" uniqKey="Viollet B" first="Benoit" last="Viollet">Benoit Viollet</name>
<name sortKey="Viollet, Benoit" sort="Viollet, Benoit" uniqKey="Viollet B" first="Benoit" last="Viollet">Benoit Viollet</name>
</country>
<country name="Canada"><region name="Ontario"><name sortKey="Fullerton, Morgan D" sort="Fullerton, Morgan D" uniqKey="Fullerton M" first="Morgan D." last="Fullerton">Morgan D. Fullerton</name>
</region>
<name sortKey="Steinberg, Gregory R" sort="Steinberg, Gregory R" uniqKey="Steinberg G" first="Gregory R." last="Steinberg">Gregory R. Steinberg</name>
</country>
<country name="Australie"><region name="Victoria (État)"><name sortKey="Kemp, Bruce E" sort="Kemp, Bruce E" uniqKey="Kemp B" first="Bruce E." last="Kemp">Bruce E. Kemp</name>
</region>
</country>
</tree>
</affiliations>
</record>
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