LymphedemaV1, France, Analysis, bibRecord, 000281

New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein

Identifieur interne : 000281 ( France/Analysis ); précédent : 000280; suivant : 000282

New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein

Auteurs : Marjorie Hubeau [France] ; Flora Ngadjeua [France] ; Anne Puel [France] ; Laura Israel [France] ; Jacqueline Feinberg [France] ; Maya Chrabieh [France] ; Kiran Belani [États-Unis] ; Christine Bodemer [France] ; Isabelle Fabre [France] ; Alessandro Plebani [Italie] ; Stéphanie Boisson-Dupuis [France, États-Unis] ; Capucine Picard [France] ; Alain Fischer [France] ; Alain Israel [France] ; Laurent Abel [France, États-Unis] ; Michel Veron [France] ; Jean-Laurent Casanova [France, États-Unis] ; Fabrice Agou [France] ; Jacinta Bustamante [France]

Source :

Blood [ 0006-4971 ] ; 2011.

RBID : PMC:3251327

Abstract

Nuclear factor-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase complex, is a critical component of the NF-κB pathway. Hypomorphic mutations in the X-linked human NEMO gene cause various forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). All known X-linked EDA-ID–causing mutations impair NEMO protein expression, folding, or both. We describe here 2 EDA-ID–causing missense mutations that affect the same residue in the CC2-LZ domain (D311N and D311G) that do not impair NEMO production or folding. Structural studies based on pull-down experiments showed a defect in noncovalent interaction with K63-linked and linear polyubiquitin chains for these mutant proteins. Functional studies on the patients' cells showed an impairment of the classic NF-κB signaling pathways after activation of 2 NEMO ubiquitin-binding–dependent receptors, the TNF and IL-1β receptors, and in the CD40-dependent NF-κB pathway. We report the first human NEMO mutations responsible for X-linked EDA-ID found to affect the polyubiquitin binding of NEMO rather than its expression and folding. These experiments demonstrate that the binding of human NEMO to polyubiquitin is essential for NF-κB activation. They also demonstrate that the normal expression and folding of NEMO do not exclude a pathogenic role for NEMO mutations in patients with EDA-ID.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251327

DOI: 10.1182/blood-2010-10-315234
PubMed: 21622647
PubMed Central: 3251327

Affiliations:

France, Italie, États-Unis
Minnesota, État de New York, Île-de-France
Paris

Links to Exploration step

PMC:3251327

Le document en format XML

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<author><name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
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<author><name sortKey="Israel, Alain" sort="Israel, Alain" uniqKey="Israel A" first="Alain" last="Israel">Alain Israel</name>
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<author><name sortKey="Abel, Laurent" sort="Abel, Laurent" uniqKey="Abel L" first="Laurent" last="Abel">Laurent Abel</name>
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<author><name sortKey="Veron, Michel" sort="Veron, Michel" uniqKey="Veron M" first="Michel" last="Veron">Michel Veron</name>
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<author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
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<author><name sortKey="Agou, Fabrice" sort="Agou, Fabrice" uniqKey="Agou F" first="Fabrice" last="Agou">Fabrice Agou</name>
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<author><name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
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<affiliation wicri:level="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein</title>
<author><name sortKey="Hubeau, Marjorie" sort="Hubeau, Marjorie" uniqKey="Hubeau M" first="Marjorie" last="Hubeau">Marjorie Hubeau</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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>
</author>
<author><name sortKey="Ngadjeua, Flora" sort="Ngadjeua, Flora" uniqKey="Ngadjeua F" first="Flora" last="Ngadjeua">Flora Ngadjeua</name>
<affiliation wicri:level="3"><nlm:aff id="aff3">Institut Pasteur, Unit of Structural and Cellular Biochemistry, Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Associée, URA 2185, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Unit of Structural and Cellular Biochemistry, Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Associée, URA 2185, 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>
</author>
<author><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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>
</author>
<author><name sortKey="Israel, Laura" sort="Israel, Laura" uniqKey="Israel L" first="Laura" last="Israel">Laura Israel</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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>
</author>
<author><name sortKey="Feinberg, Jacqueline" sort="Feinberg, Jacqueline" uniqKey="Feinberg J" first="Jacqueline" last="Feinberg">Jacqueline Feinberg</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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>
</author>
<author><name sortKey="Chrabieh, Maya" sort="Chrabieh, Maya" uniqKey="Chrabieh M" first="Maya" last="Chrabieh">Maya Chrabieh</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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>
</author>
<author><name sortKey="Belani, Kiran" sort="Belani, Kiran" uniqKey="Belani K" first="Kiran" last="Belani">Kiran Belani</name>
<affiliation wicri:level="2"><nlm:aff id="aff4">Pediatric Infectious Diseases, Children's Hospitals and Clinics Minnesota, Minneapolis, MN;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Minnesota</region>
</placeName>
<wicri:cityArea>Pediatric Infectious Diseases, Children's Hospitals and Clinics Minnesota, Minneapolis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Bodemer, Christine" sort="Bodemer, Christine" uniqKey="Bodemer C" first="Christine" last="Bodemer">Christine Bodemer</name>
<affiliation wicri:level="3"><nlm:aff id="aff5">Dermatology Unit, Necker Hospital, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Dermatology Unit, Necker Hospital, 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>
</author>
<author><name sortKey="Fabre, Isabelle" sort="Fabre, Isabelle" uniqKey="Fabre I" first="Isabelle" last="Fabre">Isabelle Fabre</name>
<affiliation wicri:level="1"><nlm:aff id="aff6">Department of Infectious Diseases, Pointe-a-Pitre Abymes Hospital, Guadeloupe, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Infectious Diseases, Pointe-a-Pitre Abymes Hospital, Guadeloupe</wicri:regionArea>
<wicri:noRegion>Guadeloupe</wicri:noRegion>
<wicri:noRegion>Guadeloupe</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Plebani, Alessandro" sort="Plebani, Alessandro" uniqKey="Plebani A" first="Alessandro" last="Plebani">Alessandro Plebani</name>
<affiliation wicri:level="1"><nlm:aff id="aff7">Department of Pediatrics and Angelo Nocivelli Institute for Molecular Medicine, University of Brescia, Brescia, Italy;</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Pediatrics and Angelo Nocivelli Institute for Molecular Medicine, University of Brescia, Brescia</wicri:regionArea>
<wicri:noRegion>Brescia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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="2"><nlm:aff id="aff8">St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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="3"><nlm:aff id="aff9">Center for the Study of Primary Immunodeficiencies, Assistance Publique–Hôpitaux de Paris (AP-HP), Necker Hospital, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Center for the Study of Primary Immunodeficiencies, Assistance Publique–Hôpitaux de Paris (AP-HP), Necker Hospital, 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="3"><nlm:aff id="aff10">Pediatric Hematology-Immunology Unit, Necker Hospital, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pediatric Hematology-Immunology Unit, Necker Hospital, 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>
</author>
<author><name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name>
<affiliation wicri:level="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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="3"><nlm:aff id="aff10">Pediatric Hematology-Immunology Unit, Necker Hospital, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pediatric Hematology-Immunology Unit, Necker Hospital, 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="3"><nlm:aff wicri:cut="; and" id="aff11">Normal and Pathologic Development of the Immune System, U768, Necker Hospital, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Normal and Pathologic Development of the Immune System, U768, Necker Hospital, 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>
</author>
<author><name sortKey="Israel, Alain" sort="Israel, Alain" uniqKey="Israel A" first="Alain" last="Israel">Alain Israel</name>
<affiliation wicri:level="3"><nlm:aff id="aff12">Molecular Signaling and Cellular Activation Unit, Unité de Recherche Associée, URA 2582, CNRS, Pasteur Institute, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Molecular Signaling and Cellular Activation Unit, Unité de Recherche Associée, URA 2582, CNRS, Pasteur Institute, 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>
</author>
<author><name sortKey="Abel, Laurent" sort="Abel, Laurent" uniqKey="Abel L" first="Laurent" last="Abel">Laurent Abel</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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="2"><nlm:aff id="aff8">St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Veron, Michel" sort="Veron, Michel" uniqKey="Veron M" first="Michel" last="Veron">Michel Veron</name>
<affiliation wicri:level="3"><nlm:aff id="aff3">Institut Pasteur, Unit of Structural and Cellular Biochemistry, Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Associée, URA 2185, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Unit of Structural and Cellular Biochemistry, Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Associée, URA 2185, 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>
</author>
<author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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="2"><nlm:aff id="aff8">St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff10">Pediatric Hematology-Immunology Unit, Necker Hospital, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pediatric Hematology-Immunology Unit, Necker Hospital, 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>
</author>
<author><name sortKey="Agou, Fabrice" sort="Agou, Fabrice" uniqKey="Agou F" first="Fabrice" last="Agou">Fabrice Agou</name>
<affiliation wicri:level="3"><nlm:aff id="aff3">Institut Pasteur, Unit of Structural and Cellular Biochemistry, Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Associée, URA 2185, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Unit of Structural and Cellular Biochemistry, Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Associée, URA 2185, 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>
</author>
<author><name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<affiliation wicri:level="3"><nlm:aff id="aff1">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm, U980, 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="3"><nlm:aff id="aff2">University Paris Descartes, Necker Medical School, Paris, France;</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Paris Descartes, Necker Medical School, 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>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Nuclear factor-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase complex, is a critical component of the NF-κB pathway. Hypomorphic mutations in the X-linked human <italic>NEMO</italic>
 gene cause various forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). All known X-linked EDA-ID–causing mutations impair NEMO protein expression, folding, or both. We describe here 2 EDA-ID–causing missense mutations that affect the same residue in the CC2-LZ domain (D311N and D311G) that do not impair NEMO production or folding. Structural studies based on pull-down experiments showed a defect in noncovalent interaction with K63-linked and linear polyubiquitin chains for these mutant proteins. Functional studies on the patients' cells showed an impairment of the classic NF-κB signaling pathways after activation of 2 NEMO ubiquitin-binding–dependent receptors, the TNF and IL-1β receptors, and in the CD40-dependent NF-κB pathway. We report the first human NEMO mutations responsible for X-linked EDA-ID found to affect the polyubiquitin binding of NEMO rather than its expression and folding. These experiments demonstrate that the binding of human NEMO to polyubiquitin is essential for NF-κB activation. They also demonstrate that the normal expression and folding of NEMO do not exclude a pathogenic role for <italic>NEMO</italic>
 mutations in patients with EDA-ID.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>Italie</li>
<li>États-Unis</li>
</country>
<region><li>Minnesota</li>
<li>État de New York</li>
<li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
</settlement>
</list>
<tree><country name="France"><region name="Île-de-France"><name sortKey="Hubeau, Marjorie" sort="Hubeau, Marjorie" uniqKey="Hubeau M" first="Marjorie" last="Hubeau">Marjorie Hubeau</name>
</region>
<name sortKey="Abel, Laurent" sort="Abel, Laurent" uniqKey="Abel L" first="Laurent" last="Abel">Laurent Abel</name>
<name sortKey="Abel, Laurent" sort="Abel, Laurent" uniqKey="Abel L" first="Laurent" last="Abel">Laurent Abel</name>
<name sortKey="Agou, Fabrice" sort="Agou, Fabrice" uniqKey="Agou F" first="Fabrice" last="Agou">Fabrice Agou</name>
<name sortKey="Bodemer, Christine" sort="Bodemer, Christine" uniqKey="Bodemer C" first="Christine" last="Bodemer">Christine Bodemer</name>
<name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
<name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Chrabieh, Maya" sort="Chrabieh, Maya" uniqKey="Chrabieh M" first="Maya" last="Chrabieh">Maya Chrabieh</name>
<name sortKey="Chrabieh, Maya" sort="Chrabieh, Maya" uniqKey="Chrabieh M" first="Maya" last="Chrabieh">Maya Chrabieh</name>
<name sortKey="Fabre, Isabelle" sort="Fabre, Isabelle" uniqKey="Fabre I" first="Isabelle" last="Fabre">Isabelle Fabre</name>
<name sortKey="Feinberg, Jacqueline" sort="Feinberg, Jacqueline" uniqKey="Feinberg J" first="Jacqueline" last="Feinberg">Jacqueline Feinberg</name>
<name sortKey="Feinberg, Jacqueline" sort="Feinberg, Jacqueline" uniqKey="Feinberg J" first="Jacqueline" last="Feinberg">Jacqueline Feinberg</name>
<name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name>
<name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name>
<name sortKey="Fischer, Alain" sort="Fischer, Alain" uniqKey="Fischer A" first="Alain" last="Fischer">Alain Fischer</name>
<name sortKey="Hubeau, Marjorie" sort="Hubeau, Marjorie" uniqKey="Hubeau M" first="Marjorie" last="Hubeau">Marjorie Hubeau</name>
<name sortKey="Israel, Alain" sort="Israel, Alain" uniqKey="Israel A" first="Alain" last="Israel">Alain Israel</name>
<name sortKey="Israel, Laura" sort="Israel, Laura" uniqKey="Israel L" first="Laura" last="Israel">Laura Israel</name>
<name sortKey="Israel, Laura" sort="Israel, Laura" uniqKey="Israel L" first="Laura" last="Israel">Laura Israel</name>
<name sortKey="Ngadjeua, Flora" sort="Ngadjeua, Flora" uniqKey="Ngadjeua F" first="Flora" last="Ngadjeua">Flora Ngadjeua</name>
<name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name>
<name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name>
<name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name>
<name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name>
<name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name>
<name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name>
<name sortKey="Veron, Michel" sort="Veron, Michel" uniqKey="Veron M" first="Michel" last="Veron">Michel Veron</name>
</country>
<country name="États-Unis"><region name="Minnesota"><name sortKey="Belani, Kiran" sort="Belani, Kiran" uniqKey="Belani K" first="Kiran" last="Belani">Kiran Belani</name>
</region>
<name sortKey="Abel, Laurent" sort="Abel, Laurent" uniqKey="Abel L" first="Laurent" last="Abel">Laurent Abel</name>
<name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
</country>
<country name="Italie"><noRegion><name sortKey="Plebani, Alessandro" sort="Plebani, Alessandro" uniqKey="Plebani A" first="Alessandro" last="Plebani">Alessandro Plebani</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/France/Analysis

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000281 | SxmlIndent | more

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Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Sante
   |area=    LymphedemaV1
   |flux=    France
   |étape=   Analysis
   |type=    RBID
   |clé=     PMC:3251327
   |texte=   New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein
}}

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       | HfdSelect -Kh $EXPLOR_AREA/Data/France/Analysis/biblio.hfd   \
       | NlmPubMed2Wicri -a LymphedemaV1

This area was generated with Dilib version V0.6.31.
Data generation: Sat Nov 4 17:40:35 2017. Site generation: Tue Feb 13 16:42:16 2024

Serveur d'exploration sur le lymphœdème

New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein

New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein

Source :

Abstract

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	Serveur d'exploration sur le lymphœdème
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