Interplay between Sumoylation and Phosphorylation for Protection against α-Synuclein Inclusions*
Identifieur interne : 000461 ( Pmc/Checkpoint ); précédent : 000460; suivant : 000462Interplay between Sumoylation and Phosphorylation for Protection against α-Synuclein Inclusions*
Auteurs : Hedieh Shahpasandzadeh ; Blagovesta Popova ; Alexandra Kleinknecht ; Paul E. Fraser ; Tiago F. Outeiro ; Gerhard H. BrausSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2014.
Abstract
Url:
DOI: 10.1074/jbc.M114.559237
PubMed: 25231978
PubMed Central: 4223324
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Interplay between Sumoylation and Phosphorylation for Protection against α-Synuclein Inclusions<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Shahpasandzadeh, Hedieh" sort="Shahpasandzadeh, Hedieh" uniqKey="Shahpasandzadeh H" first="Hedieh" last="Shahpasandzadeh">Hedieh Shahpasandzadeh</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Popova, Blagovesta" sort="Popova, Blagovesta" uniqKey="Popova B" first="Blagovesta" last="Popova">Blagovesta Popova</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kleinknecht, Alexandra" sort="Kleinknecht, Alexandra" uniqKey="Kleinknecht A" first="Alexandra" last="Kleinknecht">Alexandra Kleinknecht</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E." last="Fraser">Paul E. Fraser</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Outeiro, Tiago F" sort="Outeiro, Tiago F" uniqKey="Outeiro T" first="Tiago F." last="Outeiro">Tiago F. Outeiro</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Braus, Gerhard H" sort="Braus, Gerhard H" uniqKey="Braus G" first="Gerhard H." last="Braus">Gerhard H. Braus</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25231978</idno><idno type="pmc">4223324</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223324</idno><idno type="RBID">PMC:4223324</idno><idno type="doi">10.1074/jbc.M114.559237</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000578</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000578</idno><idno type="wicri:Area/Pmc/Curation">000578</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000578</idno><idno type="wicri:Area/Pmc/Checkpoint">000461</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000461</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Interplay between Sumoylation and Phosphorylation for Protection against α-Synuclein Inclusions<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Shahpasandzadeh, Hedieh" sort="Shahpasandzadeh, Hedieh" uniqKey="Shahpasandzadeh H" first="Hedieh" last="Shahpasandzadeh">Hedieh Shahpasandzadeh</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Popova, Blagovesta" sort="Popova, Blagovesta" uniqKey="Popova B" first="Blagovesta" last="Popova">Blagovesta Popova</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Kleinknecht, Alexandra" sort="Kleinknecht, Alexandra" uniqKey="Kleinknecht A" first="Alexandra" last="Kleinknecht">Alexandra Kleinknecht</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E." last="Fraser">Paul E. Fraser</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Outeiro, Tiago F" sort="Outeiro, Tiago F" uniqKey="Outeiro T" first="Tiago F." last="Outeiro">Tiago F. Outeiro</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Braus, Gerhard H" sort="Braus, Gerhard H" uniqKey="Braus G" first="Gerhard H." last="Braus">Gerhard H. Braus</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Phosphorylation and sumoylation are post-translational modifications of the Parkinson disease protein α-synuclein.</p><p><bold>Results:</bold> α-Synuclein inclusion clearance is impaired in yeast when sumoylation is inhibited; phosphorylation of α-synuclein can compensate SUMO impairment.</p><p><bold>Conclusion:</bold> Sumoylation stimulates autophagy clearance of α-synuclein inclusions, whereas phosphorylation promotes autophagy and proteasome degradation.</p><p><bold>Significance:</bold> A complex molecular post-translational cross-talk is required in yeast to clear toxic inclusions.</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">J Biol Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25231978</article-id><article-id pub-id-type="pmc">4223324</article-id><article-id pub-id-type="publisher-id">M114.559237</article-id><article-id pub-id-type="doi">10.1074/jbc.M114.559237</article-id><article-categories><subj-group subj-group-type="heading"><subject>Molecular Bases of Disease</subject></subj-group></article-categories><title-group><article-title>Interplay between Sumoylation and Phosphorylation for Protection against α-Synuclein Inclusions<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">Sumoylation and Phosphorylation of α-Synuclein</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Shahpasandzadeh</surname><given-names>Hedieh</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Popova</surname><given-names>Blagovesta</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="author-notes" rid="FN2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kleinknecht</surname><given-names>Alexandra</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fraser</surname><given-names>Paul E.</given-names></name><xref ref-type="aff" rid="aff3"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Outeiro</surname><given-names>Tiago F.</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="aff" rid="aff4"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Braus</surname><given-names>Gerhard H.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Institute of Microbiology and Genetics, Department of Molecular Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077 Göttingen, Germany,</aff><aff id="aff2">the<label>§</label>Center for Nanoscale Microscopy and Molecular Physiology of the Brain, D-37073 Göttingen, Germany,</aff><aff id="aff3">the<label>¶</label>Tanz Centre for Research in Neurodegenerative Diseases and Department of Medical Biophysics, University of Toronto, Ontario M5T 2S8, Canada, and</aff><aff id="aff4">the<label>‖</label>Department of Neurodegeneration and Restorative Research, University Medical Center Göttingen, D-37073 Göttingen, Germany</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> To whom correspondence should be addressed: <addr-line>Dept. of Molecular Microbiology and Genetics, Institute of Microbiology and Genetics, Georg-August-Universität Göttingen, D-37077, Göttingen, Germany.</addr-line> Tel.: <phone>49-551-393771</phone>; Fax: <fax>49-551-393330</fax>; E-mail: <email>gbraus@gwdg.de</email>.</corresp><fn fn-type="equal" id="FN2"><label>1</label><p>Both authors contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><day>7</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>17</day><month>9</month><year>2014</year></pub-date><volume>289</volume><issue>45</issue><fpage>31224</fpage><lpage>31240</lpage><history><date date-type="received"><day>21</day><month>2</month><year>2014</year></date><date date-type="rev-recd"><day>16</day><month>9</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2014</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc04514031224.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> Phosphorylation and sumoylation are post-translational modifications of the Parkinson disease protein α-synuclein.</p><p><bold>Results:</bold> α-Synuclein inclusion clearance is impaired in yeast when sumoylation is inhibited; phosphorylation of α-synuclein can compensate SUMO impairment.</p><p><bold>Conclusion:</bold> Sumoylation stimulates autophagy clearance of α-synuclein inclusions, whereas phosphorylation promotes autophagy and proteasome degradation.</p><p><bold>Significance:</bold> A complex molecular post-translational cross-talk is required in yeast to clear toxic inclusions.</p></abstract><abstract><p>Parkinson disease is associated with the progressive loss of dopaminergic neurons from the substantia nigra. The pathological hallmark of the disease is the accumulation of intracytoplasmic inclusions known as Lewy bodies that consist mainly of post-translationally modified forms of α-synuclein. Whereas phosphorylation is one of the major modifications of α-synuclein in Lewy bodies, sumoylation has recently been described. The interplay between α-synuclein phosphorylation and sumoylation is poorly understood. Here, we examined the interplay between these modifications as well as their impact on cell growth and inclusion formation in yeast. We found that α-synuclein is sumoylated <italic>in vivo</italic> at the same sites in yeast as in human cells. Impaired sumoylation resulted in reduced yeast growth combined with an increased number of cells with inclusions, suggesting that this modification plays a protective role. In addition, inhibition of sumoylation prevented autophagy-mediated aggregate clearance. A defect in α-synuclein sumoylation could be suppressed by serine 129 phosphorylation by the human G protein-coupled receptor kinase 5 (GRK5) in yeast. Phosphorylation reduced foci formation, alleviated yeast growth inhibition, and partially rescued autophagic α-synuclein degradation along with the promotion of proteasomal degradation, resulting in aggregate clearance in the absence of a small ubiquitin-like modifier. These findings suggest a complex interplay between sumoylation and phosphorylation in α-synuclein aggregate clearance, which may open new horizons for the development of therapeutic strategies for Parkinson disease.</p></abstract><kwd-group><kwd>α-Synuclein</kwd><kwd>Autophagy</kwd><kwd>Post-translational Modification</kwd><kwd>Proteasome</kwd><kwd>Yeast</kwd></kwd-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Braus, Gerhard H" sort="Braus, Gerhard H" uniqKey="Braus G" first="Gerhard H." last="Braus">Gerhard H. Braus</name><name sortKey="Fraser, Paul E" sort="Fraser, Paul E" uniqKey="Fraser P" first="Paul E." last="Fraser">Paul E. Fraser</name><name sortKey="Kleinknecht, Alexandra" sort="Kleinknecht, Alexandra" uniqKey="Kleinknecht A" first="Alexandra" last="Kleinknecht">Alexandra Kleinknecht</name><name sortKey="Outeiro, Tiago F" sort="Outeiro, Tiago F" uniqKey="Outeiro T" first="Tiago F." last="Outeiro">Tiago F. Outeiro</name><name sortKey="Popova, Blagovesta" sort="Popova, Blagovesta" uniqKey="Popova B" first="Blagovesta" last="Popova">Blagovesta Popova</name><name sortKey="Shahpasandzadeh, Hedieh" sort="Shahpasandzadeh, Hedieh" uniqKey="Shahpasandzadeh H" first="Hedieh" last="Shahpasandzadeh">Hedieh Shahpasandzadeh</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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