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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">USP9x-mediated deubiquitination of EFA6 regulates <italic>de novo</italic> tight junction assembly</title><author><name sortKey="Theard, Delphine" sort="Theard, Delphine" uniqKey="Theard D" first="Delphine" last="Théard">Delphine Théard</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Labarrade, Florian" sort="Labarrade, Florian" uniqKey="Labarrade F" first="Florian" last="Labarrade">Florian Labarrade</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Partisani, Mariagrazia" sort="Partisani, Mariagrazia" uniqKey="Partisani M" first="Mariagrazia" last="Partisani">Mariagrazia Partisani</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Milanini, Julie" sort="Milanini, Julie" uniqKey="Milanini J" first="Julie" last="Milanini">Julie Milanini</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Sakagami, Hiroyuki" sort="Sakagami, Hiroyuki" uniqKey="Sakagami H" first="Hiroyuki" last="Sakagami">Hiroyuki Sakagami</name><affiliation><nlm:aff id="a2"><institution>Department of Anatomy, Kitasato University School of Medicine</institution>, Kitasato,<country>Japan</country></nlm:aff></affiliation></author><author><name sortKey="Fon, Edward A" sort="Fon, Edward A" uniqKey="Fon E" first="Edward A" last="Fon">Edward A. Fon</name><affiliation><nlm:aff id="a3"><institution>Montreal Neurological Institute, McGill University, Montréal</institution>, Québec,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Wood, Stephen A" sort="Wood, Stephen A" uniqKey="Wood S" first="Stephen A" last="Wood">Stephen A. Wood</name><affiliation><nlm:aff id="a4"><institution>National Centre for Adult Stem Cell Research, Griffith University, Nathan</institution>, Queensland,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Franco, Michel" sort="Franco, Michel" uniqKey="Franco M" first="Michel" last="Franco">Michel Franco</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Luton, Frederic" sort="Luton, Frederic" uniqKey="Luton F" first="Frédéric" last="Luton">Frédéric Luton</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20339350</idno><idno type="pmc">2876957</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876957</idno><idno type="RBID">PMC:2876957</idno><idno type="doi">10.1038/emboj.2010.46</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000043</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000043</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">USP9x-mediated deubiquitination of EFA6 regulates <italic>de novo</italic> tight junction assembly</title><author><name sortKey="Theard, Delphine" sort="Theard, Delphine" uniqKey="Theard D" first="Delphine" last="Théard">Delphine Théard</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Labarrade, Florian" sort="Labarrade, Florian" uniqKey="Labarrade F" first="Florian" last="Labarrade">Florian Labarrade</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Partisani, Mariagrazia" sort="Partisani, Mariagrazia" uniqKey="Partisani M" first="Mariagrazia" last="Partisani">Mariagrazia Partisani</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Milanini, Julie" sort="Milanini, Julie" uniqKey="Milanini J" first="Julie" last="Milanini">Julie Milanini</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Sakagami, Hiroyuki" sort="Sakagami, Hiroyuki" uniqKey="Sakagami H" first="Hiroyuki" last="Sakagami">Hiroyuki Sakagami</name><affiliation><nlm:aff id="a2"><institution>Department of Anatomy, Kitasato University School of Medicine</institution>, Kitasato,<country>Japan</country></nlm:aff></affiliation></author><author><name sortKey="Fon, Edward A" sort="Fon, Edward A" uniqKey="Fon E" first="Edward A" last="Fon">Edward A. Fon</name><affiliation><nlm:aff id="a3"><institution>Montreal Neurological Institute, McGill University, Montréal</institution>, Québec,<country>Canada</country></nlm:aff></affiliation></author><author><name sortKey="Wood, Stephen A" sort="Wood, Stephen A" uniqKey="Wood S" first="Stephen A" last="Wood">Stephen A. Wood</name><affiliation><nlm:aff id="a4"><institution>National Centre for Adult Stem Cell Research, Griffith University, Nathan</institution>, Queensland,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Franco, Michel" sort="Franco, Michel" uniqKey="Franco M" first="Michel" last="Franco">Michel Franco</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Luton, Frederic" sort="Luton, Frederic" uniqKey="Luton F" first="Frédéric" last="Luton">Frédéric Luton</name><affiliation><nlm:aff id="a1"><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></nlm:aff></affiliation></author></analytic><series><title level="j">The EMBO Journal</title><idno type="ISSN">0261-4189</idno><idno type="eISSN">1460-2075</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In epithelial cells, the tight junction (TJ) functions as a permeability barrier and is involved in cellular differentiation and proliferation. Although many TJ proteins have been characterized, little is known about the sequence of events and temporal regulation of TJ assembly in response to adhesion cues. We report here that the deubiquitinating enzyme USP9x has a critical function in TJ biogenesis by controlling the levels of the exchange factor for Arf6 (EFA6), a protein shown to facilitate TJ formation, during a narrow temporal window preceding the establishment of cell polarity. At steady state, EFA6 is constitutively ubiquitinated and turned over by the proteasome. However, at newly forming contacts, USP9x-mediated deubiquitination protects EFA6 from proteasomal degradation, leading to a transient increase in EFA6 levels. Consistent with this model, USP9x and EFA6 transiently co-localize at primordial epithelial junctions. Furthermore, knockdown of either EFA6 or USP9x impairs TJ biogenesis and EFA6 overexpression rescues TJ biogenesis in USP9x-knockdown cells. As the loss of cell polarity is a critical event in the metastatic spread of cancer, these findings may help to understand the pathology of human carcinomas.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">EMBO J</journal-id><journal-title-group><journal-title>The EMBO Journal</journal-title></journal-title-group><issn pub-type="ppub">0261-4189</issn><issn pub-type="epub">1460-2075</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20339350</article-id><article-id pub-id-type="pmc">2876957</article-id><article-id pub-id-type="pii">emboj201046</article-id><article-id pub-id-type="doi">10.1038/emboj.2010.46</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>USP9x-mediated deubiquitination of EFA6 regulates <italic>de novo</italic> tight junction assembly</article-title><alt-title alt-title-type="short">USP9x regulates tight junction via EFA6</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Théard</surname><given-names>Delphine</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Labarrade</surname><given-names>Florian</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Partisani</surname><given-names>Mariagrazia</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Milanini</surname><given-names>Julie</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sakagami</surname><given-names>Hiroyuki</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Fon</surname><given-names>Edward A</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Wood</surname><given-names>Stephen A</given-names></name><xref ref-type="aff" rid="a4">4</xref></contrib><contrib contrib-type="author"><name><surname>Franco</surname><given-names>Michel</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Luton</surname><given-names>Frédéric</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref></contrib><aff id="a1"><label>1</label><institution>CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis</institution>, Valbonne,<country>France</country></aff><aff id="a2"><label>2</label><institution>Department of Anatomy, Kitasato University School of Medicine</institution>, Kitasato,<country>Japan</country></aff><aff id="a3"><label>3</label><institution>Montreal Neurological Institute, McGill University, Montréal</institution>, Québec,<country>Canada</country></aff><aff id="a4"><label>4</label><institution>National Centre for Adult Stem Cell Research, Griffith University, Nathan</institution>, Queensland,<country>Australia</country></aff></contrib-group><author-notes><corresp id="c1"><label>a</label>CNRS UNSA UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, 660 Route des Lucioles, Valbonne 6560, France. Tel.: +33 04 93 95 77 70; Fax: +33 04 93 95 77 08; E-mail: <email>luton@ipmc.cnrs.fr</email></corresp></author-notes><pub-date pub-type="ppub"><day>05</day><month>05</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>25</day><month>03</month><year>2010</year></pub-date><volume>29</volume><issue>9</issue><fpage>1499</fpage><lpage>1509</lpage><history><date date-type="received"><day>15</day><month>02</month><year>2010</year></date><date date-type="accepted"><day>03</day><month>03</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2010, European Molecular Biology Organization</copyright-statement><copyright-year>2010</copyright-year><copyright-holder>European Molecular Biology Organization</copyright-holder></permissions><abstract><p>In epithelial cells, the tight junction (TJ) functions as a permeability barrier and is involved in cellular differentiation and proliferation. Although many TJ proteins have been characterized, little is known about the sequence of events and temporal regulation of TJ assembly in response to adhesion cues. We report here that the deubiquitinating enzyme USP9x has a critical function in TJ biogenesis by controlling the levels of the exchange factor for Arf6 (EFA6), a protein shown to facilitate TJ formation, during a narrow temporal window preceding the establishment of cell polarity. At steady state, EFA6 is constitutively ubiquitinated and turned over by the proteasome. However, at newly forming contacts, USP9x-mediated deubiquitination protects EFA6 from proteasomal degradation, leading to a transient increase in EFA6 levels. Consistent with this model, USP9x and EFA6 transiently co-localize at primordial epithelial junctions. Furthermore, knockdown of either EFA6 or USP9x impairs TJ biogenesis and EFA6 overexpression rescues TJ biogenesis in USP9x-knockdown cells. As the loss of cell polarity is a critical event in the metastatic spread of cancer, these findings may help to understand the pathology of human carcinomas.</p></abstract><kwd-group><kwd>EFA6</kwd><kwd>proteasome</kwd><kwd>tight junction</kwd><kwd>USP9x</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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