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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>Drosophila</italic> Ndfip is a novel regulator of Notch signaling</title><author><name sortKey="Dalton, H E" sort="Dalton, H E" uniqKey="Dalton H" first="H E" last="Dalton">H E Dalton</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Denton, D" sort="Denton, D" uniqKey="Denton D" first="D" last="Denton">D. Denton</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Foot, N J" sort="Foot, N J" uniqKey="Foot N" first="N J" last="Foot">N J Foot</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Ho, K" sort="Ho, K" uniqKey="Ho K" first="K" last="Ho">K. Ho</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mills, K" sort="Mills, K" uniqKey="Mills K" first="K" last="Mills">K. Mills</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Brou, C" sort="Brou, C" uniqKey="Brou C" first="C" last="Brou">C. Brou</name><affiliation><nlm:aff id="aff2"><institution>Unité de Signalisation Moléculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Kumar, S" sort="Kumar, S" uniqKey="Kumar S" first="S" last="Kumar">S. Kumar</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Department of Medicine, University of Adelaide, North Terrace</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20966964</idno><idno type="pmc">3131964</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131964</idno><idno type="RBID">PMC:3131964</idno><idno type="doi">10.1038/cdd.2010.130</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000042</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000042</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Drosophila</italic> Ndfip is a novel regulator of Notch signaling</title><author><name sortKey="Dalton, H E" sort="Dalton, H E" uniqKey="Dalton H" first="H E" last="Dalton">H E Dalton</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Denton, D" sort="Denton, D" uniqKey="Denton D" first="D" last="Denton">D. Denton</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Foot, N J" sort="Foot, N J" uniqKey="Foot N" first="N J" last="Foot">N J Foot</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Ho, K" sort="Ho, K" uniqKey="Ho K" first="K" last="Ho">K. Ho</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Mills, K" sort="Mills, K" uniqKey="Mills K" first="K" last="Mills">K. Mills</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author><author><name sortKey="Brou, C" sort="Brou, C" uniqKey="Brou C" first="C" last="Brou">C. Brou</name><affiliation><nlm:aff id="aff2"><institution>Unité de Signalisation Moléculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur</institution>, Paris,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Kumar, S" sort="Kumar, S" uniqKey="Kumar S" first="S" last="Kumar">S. Kumar</name><affiliation><nlm:aff id="aff1"><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Department of Medicine, University of Adelaide, North Terrace</institution>, Adelaide, SA,<country>Australia</country></nlm:aff></affiliation></author></analytic><series><title level="j">Cell Death and Differentiation</title><idno type="ISSN">1350-9047</idno><idno type="eISSN">1476-5403</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 the <italic>Drosophila</italic> wing, the Nedd4 ubiquitin ligases (E3s), dNedd4 and Su(dx), are important negative regulators of Notch signaling; they ubiquitinate Notch, promoting its endocytosis and turnover. Here, we show that <italic>Drosophila</italic> Nedd4 family interacting protein (dNdfip) interacts with the <italic>Drosophila</italic> Nedd4-like E3s. dNdfip expression dramatically enhances dNedd4 and Su(dx)-mediated wing phenotypes and further disrupts Notch signaling. dNdfip colocalizes with Notch in wing imaginal discs and with the late endosomal marker Rab7 in cultured cells. In addition, dNdfip expression in the wing leads to ectopic Notch signaling. Supporting this, expression of dNdfip suppressed <italic>Notch</italic><sup>+/−</sup> wing phenotype and knockdown of dNdfip enhanced the <italic>Notch</italic><sup>+/−</sup> wing phenotype. The increase in Notch activity by dNdfip is ligand independent as dNdfip expression also suppressed <italic>deltex</italic> RNAi and <italic>Serrate</italic><sup>+/−</sup> wing phenotypes. The opposing effects of dNdfip expression on Notch signaling and its late endosomal localization support a model whereby dNdfip promotes localization of Notch to the limiting membrane of late endosomes allowing for activation, similar to the model previously shown with ectopic Deltex expression. When dNedd4 or Su(dx) are also present, dNdfip promotes their activity in Notch ubiquitination and internalization to the lysosomal lumen for degradation.</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">Cell Death Differ</journal-id><journal-title-group><journal-title>Cell Death and Differentiation</journal-title></journal-title-group><issn pub-type="ppub">1350-9047</issn><issn pub-type="epub">1476-5403</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20966964</article-id><article-id pub-id-type="pmc">3131964</article-id><article-id pub-id-type="pii">cdd2010130</article-id><article-id pub-id-type="doi">10.1038/cdd.2010.130</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Paper</subject></subj-group></article-categories><title-group><article-title><italic>Drosophila</italic> Ndfip is a novel regulator of Notch signaling</article-title><alt-title alt-title-type="running">dNdfip modulates Nedd4 regulation of Notch</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Dalton</surname><given-names>H E</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="author-notes" rid="note1"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Denton</surname><given-names>D</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="author-notes" rid="note1"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Foot</surname><given-names>N J</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ho</surname><given-names>K</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mills</surname><given-names>K</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Brou</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kumar</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><aff id="aff1"><label>1</label><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Adelaide, SA,<country>Australia</country></aff><aff id="aff2"><label>2</label><institution>Unité de Signalisation Moléculaire et Activation Cellulaire, URA 2582, CNRS, Institut Pasteur</institution>, Paris,<country>France</country></aff><aff id="aff3"><label>3</label><institution>Department of Medicine, University of Adelaide, North Terrace</institution>, Adelaide, SA,<country>Australia</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label><institution>Division of Haematology, Centre for Cancer Biology, SA Pathology</institution>, Frome Road, Adelaide, SA 5000, <country>Australia</country>. E-mail: <email>sharad.kumar@health.sa.gov.au</email></corresp><fn fn-type="present-address" id="note1"><label>4</label><p>These authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><month>07</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>22</day><month>10</month><year>2010</year></pub-date><volume>18</volume><issue>7</issue><fpage>1150</fpage><lpage>1160</lpage><history><date date-type="received"><day>17</day><month>06</month><year>2010</year></date><date date-type="rev-recd"><day>16</day><month>09</month><year>2010</year></date><date date-type="accepted"><day>21</day><month>09</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2011 Macmillan Publishers Limited</copyright-statement><copyright-year>2011</copyright-year><copyright-holder>Macmillan Publishers Limited</copyright-holder></permissions><abstract><p>In the <italic>Drosophila</italic> wing, the Nedd4 ubiquitin ligases (E3s), dNedd4 and Su(dx), are important negative regulators of Notch signaling; they ubiquitinate Notch, promoting its endocytosis and turnover. Here, we show that <italic>Drosophila</italic> Nedd4 family interacting protein (dNdfip) interacts with the <italic>Drosophila</italic> Nedd4-like E3s. dNdfip expression dramatically enhances dNedd4 and Su(dx)-mediated wing phenotypes and further disrupts Notch signaling. dNdfip colocalizes with Notch in wing imaginal discs and with the late endosomal marker Rab7 in cultured cells. In addition, dNdfip expression in the wing leads to ectopic Notch signaling. Supporting this, expression of dNdfip suppressed <italic>Notch</italic><sup>+/−</sup> wing phenotype and knockdown of dNdfip enhanced the <italic>Notch</italic><sup>+/−</sup> wing phenotype. The increase in Notch activity by dNdfip is ligand independent as dNdfip expression also suppressed <italic>deltex</italic> RNAi and <italic>Serrate</italic><sup>+/−</sup> wing phenotypes. The opposing effects of dNdfip expression on Notch signaling and its late endosomal localization support a model whereby dNdfip promotes localization of Notch to the limiting membrane of late endosomes allowing for activation, similar to the model previously shown with ectopic Deltex expression. When dNedd4 or Su(dx) are also present, dNdfip promotes their activity in Notch ubiquitination and internalization to the lysosomal lumen for degradation.</p></abstract><kwd-group><kwd>Nedd4</kwd><kwd>ubiquitination</kwd><kwd>Ndfips</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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