MDM4 is a key therapeutic target in cutaneous melanoma
Identifieur interne : 005321 ( Main/Exploration ); précédent : 005320; suivant : 005322MDM4 is a key therapeutic target in cutaneous melanoma
Auteurs : Agnieszka Gembarska [Belgique] ; Flavie Luciani [Belgique] ; Clare Fedele [Australie] ; Elisabeth A. Russell [États-Unis] ; Michael Dewaele [Belgique] ; Stéphanie Villar [France] ; Aleksandra Zwolinska [Belgique] ; Sue Haupt [Australie] ; Job De Lange [Pays-Bas] ; Dana Yip [États-Unis] ; James Goydos [États-Unis] ; Jody J. Haigh [Belgique] ; Ygal Haupt [Australie] ; Lionel Larue [France] ; Aart Jochemsen [Pays-Bas] ; Hubing Shi [États-Unis] ; Gatien Moriceau [États-Unis] ; Roger S. Lo [États-Unis] ; Ghanem Ghanem [Belgique] ; Mark Shackleton [Australie] ; Federico Bernal [États-Unis] ; Jean-Christophe Marine [Belgique]Source :
- Nature medicine [ 1078-8956 ] ; 2012.
Abstract
The inactivation of the p53 tumor suppressor pathway, which often occurs through mutations in
Url:
DOI: 10.1038/nm.2863
PubMed: 22820643
PubMed Central: 3744207
Affiliations:
- Australie, Belgique, France, Pays-Bas, États-Unis
- Auvergne-Rhône-Alpes, Californie, Hollande-Méridionale, Maryland, New Jersey, Province de Flandre-Orientale, Rhône-Alpes, Région de Bruxelles-Capitale, Région flamande, Victoria (État)
- Bruxelles, Gand, Leyde, Lyon, Melbourne, Orsay
- Université de Gand, Université de Melbourne
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type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Zwolinska, Aleksandra" sort="Zwolinska, Aleksandra" uniqKey="Zwolinska A" first="Aleksandra" last="Zwolinska">Aleksandra Zwolinska</name><affiliation wicri:level="1"><nlm:aff id="A1">Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Haupt, Sue" sort="Haupt, Sue" uniqKey="Haupt S" first="Sue" last="Haupt">Sue Haupt</name><affiliation wicri:level="4"><nlm:aff id="A7">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Peter MacCallum Cancer Centre, Research Division, East Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Research Division, East Melbourne</wicri:regionArea><wicri:noRegion>East Melbourne</wicri:noRegion></affiliation></author><author><name sortKey="De Lange, Job" sort="De Lange, Job" uniqKey="De Lange J" first="Job" last="De Lange">Job De Lange</name><affiliation wicri:level="3"><nlm:aff id="A9">Department of Molecular Cell Biology, University Medical Centre, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Molecular Cell Biology, University Medical Centre, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Yip, Dana" sort="Yip, Dana" uniqKey="Yip D" first="Dana" last="Yip">Dana Yip</name><affiliation wicri:level="2"><nlm:aff id="A10">Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Goydos, James" sort="Goydos, James" uniqKey="Goydos J" first="James" last="Goydos">James Goydos</name><affiliation wicri:level="2"><nlm:aff id="A10">Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. Haigh</name><affiliation wicri:level="1"><nlm:aff id="A11">Vascular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vascular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, Ghent</wicri:regionArea><wicri:noRegion>Ghent</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A12">Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Biomedical Molecular Biology, Ghent University, Ghent</wicri:regionArea><orgName type="university">Université de Gand</orgName><placeName><settlement type="city">Gand</settlement><region>Région flamande</region><region type="district" nuts="2">Province de Flandre-Orientale</region></placeName></affiliation></author><author><name sortKey="Haupt, Ygal" sort="Haupt, Ygal" uniqKey="Haupt Y" first="Ygal" last="Haupt">Ygal Haupt</name><affiliation wicri:level="4"><nlm:aff id="A7">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Peter MacCallum Cancer Centre, Research Division, East Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Research Division, East Melbourne</wicri:regionArea><wicri:noRegion>East Melbourne</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A13">Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Larue, Lionel" sort="Larue, Lionel" uniqKey="Larue L" first="Lionel" last="Larue">Lionel Larue</name><affiliation wicri:level="3"><nlm:aff id="A14">Curie Institute, Developmental Genetics of Melanocytes, Centre National de la Recherche Scientifique (CNRS) UMR3347, Institut National de la Santé et de la Recherche Médicale (INSERM) U1021, Orsay, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Curie Institute, Developmental Genetics of Melanocytes, Centre National de la Recherche Scientifique (CNRS) UMR3347, Institut National de la Santé et de la Recherche Médicale (INSERM) U1021, Orsay</wicri:regionArea><placeName><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Jochemsen, Aart" sort="Jochemsen, Aart" uniqKey="Jochemsen A" first="Aart" last="Jochemsen">Aart Jochemsen</name><affiliation wicri:level="3"><nlm:aff id="A9">Department of Molecular Cell Biology, University Medical Centre, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Molecular Cell Biology, University Medical Centre, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Shi, Hubing" sort="Shi, Hubing" uniqKey="Shi H" first="Hubing" last="Shi">Hubing Shi</name><affiliation wicri:level="2"><nlm:aff id="A15">Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A16">Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Moriceau, Gatien" sort="Moriceau, Gatien" uniqKey="Moriceau G" first="Gatien" last="Moriceau">Gatien Moriceau</name><affiliation wicri:level="2"><nlm:aff id="A15">Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A16">Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lo, Roger S" sort="Lo, Roger S" uniqKey="Lo R" first="Roger S" last="Lo">Roger S. Lo</name><affiliation wicri:level="2"><nlm:aff id="A15">Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A16">Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ghanem, Ghanem" sort="Ghanem, Ghanem" uniqKey="Ghanem G" first="Ghanem" last="Ghanem">Ghanem Ghanem</name><affiliation wicri:level="3"><nlm:aff id="A17">Institute Jules Bordet, Brussels, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Institute Jules Bordet, Brussels</wicri:regionArea><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region></placeName></affiliation></author><author><name sortKey="Shackleton, Mark" sort="Shackleton, Mark" uniqKey="Shackleton M" first="Mark" last="Shackleton">Mark Shackleton</name><affiliation wicri:level="1"><nlm:aff id="A3">Melanoma Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melanoma Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne</wicri:regionArea><wicri:noRegion>East Melbourne</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A4">Department of Pathology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A7">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville</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="Bernal, Federico" sort="Bernal, Federico" uniqKey="Bernal F" first="Federico" last="Bernal">Federico Bernal</name><affiliation wicri:level="2"><nlm:aff id="A5">Metabolism Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Metabolism Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Marine, Jean Christophe" sort="Marine, Jean Christophe" uniqKey="Marine J" first="Jean-Christophe" last="Marine">Jean-Christophe Marine</name><affiliation wicri:level="1"><nlm:aff id="A1">Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22820643</idno><idno type="pmc">3744207</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744207</idno><idno 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therapeutic target in cutaneous melanoma</title><author><name sortKey="Gembarska, Agnieszka" sort="Gembarska, Agnieszka" uniqKey="Gembarska A" first="Agnieszka" last="Gembarska">Agnieszka Gembarska</name><affiliation wicri:level="1"><nlm:aff id="A1">Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Luciani, Flavie" sort="Luciani, Flavie" uniqKey="Luciani F" first="Flavie" last="Luciani">Flavie Luciani</name><affiliation wicri:level="1"><nlm:aff id="A1">Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Fedele, Clare" sort="Fedele, Clare" uniqKey="Fedele C" first="Clare" last="Fedele">Clare Fedele</name><affiliation wicri:level="1"><nlm:aff id="A3">Melanoma Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melanoma Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne</wicri:regionArea><wicri:noRegion>East Melbourne</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A4">Department of Pathology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville</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="Russell, Elisabeth A" sort="Russell, Elisabeth A" uniqKey="Russell E" first="Elisabeth A" last="Russell">Elisabeth A. Russell</name><affiliation wicri:level="2"><nlm:aff id="A5">Metabolism Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Metabolism Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Dewaele, Michael" sort="Dewaele, Michael" uniqKey="Dewaele M" first="Michael" last="Dewaele">Michael Dewaele</name><affiliation wicri:level="1"><nlm:aff id="A1">Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Villar, Stephanie" sort="Villar, Stephanie" uniqKey="Villar S" first="Stéphanie" last="Villar">Stéphanie Villar</name><affiliation wicri:level="3"><nlm:aff id="A6">International Agency for Research on Cancer (IARC/CIRC), Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>International Agency for Research on Cancer (IARC/CIRC), Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Zwolinska, Aleksandra" sort="Zwolinska, Aleksandra" uniqKey="Zwolinska A" first="Aleksandra" last="Zwolinska">Aleksandra Zwolinska</name><affiliation wicri:level="1"><nlm:aff id="A1">Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Haupt, Sue" sort="Haupt, Sue" uniqKey="Haupt S" first="Sue" last="Haupt">Sue Haupt</name><affiliation wicri:level="4"><nlm:aff id="A7">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Peter MacCallum Cancer Centre, Research Division, East Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Research Division, East Melbourne</wicri:regionArea><wicri:noRegion>East Melbourne</wicri:noRegion></affiliation></author><author><name sortKey="De Lange, Job" sort="De Lange, Job" uniqKey="De Lange J" first="Job" last="De Lange">Job De Lange</name><affiliation wicri:level="3"><nlm:aff id="A9">Department of Molecular Cell Biology, University Medical Centre, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Molecular Cell Biology, University Medical Centre, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Yip, Dana" sort="Yip, Dana" uniqKey="Yip D" first="Dana" last="Yip">Dana Yip</name><affiliation wicri:level="2"><nlm:aff id="A10">Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Goydos, James" sort="Goydos, James" uniqKey="Goydos J" first="James" last="Goydos">James Goydos</name><affiliation wicri:level="2"><nlm:aff id="A10">Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Cancer Institute of New Jersey, New Brunswick, New Jersey</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. Haigh</name><affiliation wicri:level="1"><nlm:aff id="A11">Vascular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Vascular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, Ghent</wicri:regionArea><wicri:noRegion>Ghent</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A12">Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Department of Biomedical Molecular Biology, Ghent University, Ghent</wicri:regionArea><orgName type="university">Université de Gand</orgName><placeName><settlement type="city">Gand</settlement><region>Région flamande</region><region type="district" nuts="2">Province de Flandre-Orientale</region></placeName></affiliation></author><author><name sortKey="Haupt, Ygal" sort="Haupt, Ygal" uniqKey="Haupt Y" first="Ygal" last="Haupt">Ygal Haupt</name><affiliation wicri:level="4"><nlm:aff id="A7">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A8">Peter MacCallum Cancer Centre, Research Division, East Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, Research Division, East Melbourne</wicri:regionArea><wicri:noRegion>East Melbourne</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A13">Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Monash University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Larue, Lionel" sort="Larue, Lionel" uniqKey="Larue L" first="Lionel" last="Larue">Lionel Larue</name><affiliation wicri:level="3"><nlm:aff id="A14">Curie Institute, Developmental Genetics of Melanocytes, Centre National de la Recherche Scientifique (CNRS) UMR3347, Institut National de la Santé et de la Recherche Médicale (INSERM) U1021, Orsay, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Curie Institute, Developmental Genetics of Melanocytes, Centre National de la Recherche Scientifique (CNRS) UMR3347, Institut National de la Santé et de la Recherche Médicale (INSERM) U1021, Orsay</wicri:regionArea><placeName><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Jochemsen, Aart" sort="Jochemsen, Aart" uniqKey="Jochemsen A" first="Aart" last="Jochemsen">Aart Jochemsen</name><affiliation wicri:level="3"><nlm:aff id="A9">Department of Molecular Cell Biology, University Medical Centre, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Molecular Cell Biology, University Medical Centre, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Shi, Hubing" sort="Shi, Hubing" uniqKey="Shi H" first="Hubing" last="Shi">Hubing Shi</name><affiliation wicri:level="2"><nlm:aff id="A15">Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A16">Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Moriceau, Gatien" sort="Moriceau, Gatien" uniqKey="Moriceau G" first="Gatien" last="Moriceau">Gatien Moriceau</name><affiliation wicri:level="2"><nlm:aff id="A15">Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A16">Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Lo, Roger S" sort="Lo, Roger S" uniqKey="Lo R" first="Roger S" last="Lo">Roger S. Lo</name><affiliation wicri:level="2"><nlm:aff id="A15">Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine (Division of Dermatology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A16">Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Medical Pharmacology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Ghanem, Ghanem" sort="Ghanem, Ghanem" uniqKey="Ghanem G" first="Ghanem" last="Ghanem">Ghanem Ghanem</name><affiliation wicri:level="3"><nlm:aff id="A17">Institute Jules Bordet, Brussels, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Institute Jules Bordet, Brussels</wicri:regionArea><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region></placeName></affiliation></author><author><name sortKey="Shackleton, Mark" sort="Shackleton, Mark" uniqKey="Shackleton M" first="Mark" last="Shackleton">Mark Shackleton</name><affiliation wicri:level="1"><nlm:aff id="A3">Melanoma Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melanoma Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne</wicri:regionArea><wicri:noRegion>East Melbourne</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="A4">Department of Pathology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, The University of Melbourne, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A7">Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville</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="Bernal, Federico" sort="Bernal, Federico" uniqKey="Bernal F" first="Federico" last="Bernal">Federico Bernal</name><affiliation wicri:level="2"><nlm:aff id="A5">Metabolism Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Metabolism Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Marine, Jean Christophe" sort="Marine, Jean Christophe" uniqKey="Marine J" first="Jean-Christophe" last="Marine">Jean-Christophe Marine</name><affiliation wicri:level="1"><nlm:aff id="A1">Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for the Biology of Disease, Laboratory for Molecular Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven, Belgium</nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea>Center for Human Genetics, Katholieke Universiteit (KU) Leuven, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature medicine</title><idno type="ISSN">1078-8956</idno><idno type="eISSN">1546-170X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The inactivation of the p53 tumor suppressor pathway, which often occurs through mutations in <italic>TP53</italic> (encoding tumor protein 53) is a common step in human cancer. However, in melanoma—a highly chemotherapy-resistant disease—<italic>TP53</italic> mutations are rare, raising the possibility that this cancer uses alternative ways to overcome p53-mediated tumor suppression. Here we show that Mdm4 p53 binding protein homolog (MDM4), a negative regulator of p53, is upregulated in a substantial proportion (∼65%) of stage I–IV human melanomas and that melanocyte-specific Mdm4 overexpression enhanced tumorigenesis in a mouse model of melanoma induced by the oncogene <italic>Nras</italic>. MDM4 promotes the survival of human metastatic melanoma by antagonizing p53 proapoptotic function. Notably, inhibition of the MDM4-p53 interaction restored p53 function in melanoma cells, resulting in increased sensitivity to cytotoxic chemotherapy and to inhibitors of the <italic>BRAF</italic> (V600E) oncogene. Our results identify MDM4 as a key determinant of impaired p53 function in human melanoma and designate MDM4 as a promising target for antimelanoma combination therapy.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>Belgique</li><li>France</li><li>Pays-Bas</li><li>États-Unis</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Californie</li><li>Hollande-Méridionale</li><li>Maryland</li><li>New Jersey</li><li>Province de Flandre-Orientale</li><li>Rhône-Alpes</li><li>Région de Bruxelles-Capitale</li><li>Région flamande</li><li>Victoria (État)</li></region><settlement><li>Bruxelles</li><li>Gand</li><li>Leyde</li><li>Lyon</li><li>Melbourne</li><li>Orsay</li></settlement><orgName><li>Université de Gand</li><li>Université de Melbourne</li></orgName></list><tree><country name="Belgique"><noRegion><name sortKey="Gembarska, Agnieszka" sort="Gembarska, Agnieszka" uniqKey="Gembarska A" first="Agnieszka" last="Gembarska">Agnieszka Gembarska</name></noRegion><name sortKey="Dewaele, Michael" sort="Dewaele, Michael" uniqKey="Dewaele M" first="Michael" last="Dewaele">Michael Dewaele</name><name sortKey="Dewaele, Michael" sort="Dewaele, Michael" uniqKey="Dewaele M" first="Michael" last="Dewaele">Michael Dewaele</name><name sortKey="Gembarska, Agnieszka" sort="Gembarska, Agnieszka" uniqKey="Gembarska A" first="Agnieszka" last="Gembarska">Agnieszka Gembarska</name><name sortKey="Ghanem, Ghanem" sort="Ghanem, Ghanem" uniqKey="Ghanem G" first="Ghanem" last="Ghanem">Ghanem Ghanem</name><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. Haigh</name><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. Haigh</name><name sortKey="Luciani, Flavie" sort="Luciani, Flavie" uniqKey="Luciani F" first="Flavie" last="Luciani">Flavie Luciani</name><name sortKey="Luciani, Flavie" sort="Luciani, Flavie" uniqKey="Luciani F" first="Flavie" last="Luciani">Flavie Luciani</name><name sortKey="Marine, Jean Christophe" sort="Marine, Jean Christophe" uniqKey="Marine J" first="Jean-Christophe" last="Marine">Jean-Christophe Marine</name><name sortKey="Marine, Jean Christophe" sort="Marine, Jean Christophe" uniqKey="Marine J" first="Jean-Christophe" last="Marine">Jean-Christophe Marine</name><name sortKey="Zwolinska, Aleksandra" sort="Zwolinska, Aleksandra" uniqKey="Zwolinska A" first="Aleksandra" last="Zwolinska">Aleksandra Zwolinska</name><name sortKey="Zwolinska, Aleksandra" sort="Zwolinska, Aleksandra" uniqKey="Zwolinska A" first="Aleksandra" last="Zwolinska">Aleksandra Zwolinska</name></country><country name="Australie"><noRegion><name sortKey="Fedele, Clare" sort="Fedele, Clare" uniqKey="Fedele C" first="Clare" last="Fedele">Clare Fedele</name></noRegion><name sortKey="Fedele, Clare" sort="Fedele, Clare" uniqKey="Fedele C" first="Clare" last="Fedele">Clare Fedele</name><name sortKey="Haupt, Sue" sort="Haupt, Sue" uniqKey="Haupt S" first="Sue" last="Haupt">Sue Haupt</name><name sortKey="Haupt, Sue" sort="Haupt, Sue" uniqKey="Haupt S" first="Sue" last="Haupt">Sue Haupt</name><name sortKey="Haupt, Ygal" sort="Haupt, Ygal" uniqKey="Haupt Y" first="Ygal" last="Haupt">Ygal Haupt</name><name sortKey="Haupt, Ygal" sort="Haupt, Ygal" uniqKey="Haupt Y" first="Ygal" last="Haupt">Ygal Haupt</name><name sortKey="Haupt, Ygal" sort="Haupt, Ygal" uniqKey="Haupt Y" first="Ygal" last="Haupt">Ygal Haupt</name><name sortKey="Shackleton, Mark" sort="Shackleton, Mark" uniqKey="Shackleton M" first="Mark" last="Shackleton">Mark Shackleton</name><name sortKey="Shackleton, Mark" sort="Shackleton, Mark" uniqKey="Shackleton M" first="Mark" last="Shackleton">Mark Shackleton</name><name sortKey="Shackleton, Mark" sort="Shackleton, Mark" uniqKey="Shackleton M" first="Mark" last="Shackleton">Mark Shackleton</name></country><country name="États-Unis"><region name="Maryland"><name sortKey="Russell, Elisabeth A" sort="Russell, Elisabeth A" uniqKey="Russell E" first="Elisabeth A" last="Russell">Elisabeth A. Russell</name></region><name sortKey="Bernal, Federico" sort="Bernal, Federico" uniqKey="Bernal F" first="Federico" last="Bernal">Federico Bernal</name><name sortKey="Goydos, James" sort="Goydos, James" uniqKey="Goydos J" first="James" last="Goydos">James Goydos</name><name sortKey="Lo, Roger S" sort="Lo, Roger S" uniqKey="Lo R" first="Roger S" last="Lo">Roger S. Lo</name><name sortKey="Lo, Roger S" sort="Lo, Roger S" uniqKey="Lo R" first="Roger S" last="Lo">Roger S. Lo</name><name sortKey="Moriceau, Gatien" sort="Moriceau, Gatien" uniqKey="Moriceau G" first="Gatien" last="Moriceau">Gatien Moriceau</name><name sortKey="Moriceau, Gatien" sort="Moriceau, Gatien" uniqKey="Moriceau G" first="Gatien" last="Moriceau">Gatien Moriceau</name><name sortKey="Shi, Hubing" sort="Shi, Hubing" uniqKey="Shi H" first="Hubing" last="Shi">Hubing Shi</name><name sortKey="Shi, Hubing" sort="Shi, Hubing" uniqKey="Shi H" first="Hubing" last="Shi">Hubing Shi</name><name sortKey="Yip, Dana" sort="Yip, Dana" uniqKey="Yip D" first="Dana" last="Yip">Dana Yip</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Villar, Stephanie" sort="Villar, Stephanie" uniqKey="Villar S" first="Stéphanie" last="Villar">Stéphanie Villar</name></region><name sortKey="Larue, Lionel" sort="Larue, Lionel" uniqKey="Larue L" first="Lionel" last="Larue">Lionel Larue</name></country><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="De Lange, Job" sort="De Lange, Job" uniqKey="De Lange J" first="Job" last="De Lange">Job De Lange</name></region><name sortKey="Jochemsen, Aart" sort="Jochemsen, Aart" uniqKey="Jochemsen A" first="Aart" last="Jochemsen">Aart Jochemsen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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