Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation*
Identifieur interne : 000474 ( Pmc/Corpus ); précédent : 000473; suivant : 000475Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation*
Auteurs : Magnus E. Jakobsson ; Anders Moen ; Luc Bousset ; Wolfgang Egge-Jacobsen ; Stefan Kernstock ; Ronald Melki ; P L FalnesSource :
- The Journal of Biological Chemistry [ 0021-9258 ] ; 2013.
Abstract
Url:
DOI: 10.1074/jbc.M113.483248
PubMed: 23921388
PubMed Central: 3784692
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Jakobsson, Magnus E" sort="Jakobsson, Magnus E" uniqKey="Jakobsson M" first="Magnus E." last="Jakobsson">Magnus E. Jakobsson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Moen, Anders" sort="Moen, Anders" uniqKey="Moen A" first="Anders" last="Moen">Anders Moen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Egge Jacobsen, Wolfgang" sort="Egge Jacobsen, Wolfgang" uniqKey="Egge Jacobsen W" first="Wolfgang" last="Egge-Jacobsen">Wolfgang Egge-Jacobsen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kernstock, Stefan" sort="Kernstock, Stefan" uniqKey="Kernstock S" first="Stefan" last="Kernstock">Stefan Kernstock</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Falnes, P L" sort="Falnes, P L" uniqKey="Falnes P" first="P L" last="Falnes">P L Falnes</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23921388</idno><idno type="pmc">3784692</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784692</idno><idno type="RBID">PMC:3784692</idno><idno type="doi">10.1074/jbc.M113.483248</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000474</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000474</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></title><author><name sortKey="Jakobsson, Magnus E" sort="Jakobsson, Magnus E" uniqKey="Jakobsson M" first="Magnus E." last="Jakobsson">Magnus E. Jakobsson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Moen, Anders" sort="Moen, Anders" uniqKey="Moen A" first="Anders" last="Moen">Anders Moen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bousset, Luc" sort="Bousset, Luc" uniqKey="Bousset L" first="Luc" last="Bousset">Luc Bousset</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Egge Jacobsen, Wolfgang" sort="Egge Jacobsen, Wolfgang" uniqKey="Egge Jacobsen W" first="Wolfgang" last="Egge-Jacobsen">Wolfgang Egge-Jacobsen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kernstock, Stefan" sort="Kernstock, Stefan" uniqKey="Kernstock S" first="Stefan" last="Kernstock">Stefan Kernstock</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Melki, Ronald" sort="Melki, Ronald" uniqKey="Melki R" first="Ronald" last="Melki">Ronald Melki</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Falnes, P L" sort="Falnes, P L" uniqKey="Falnes P" first="P L" last="Falnes">P L Falnes</name><affiliation><nlm:aff id="aff1"></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="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> The function of many proteins is regulated through post-translational methylation.</p><p><bold>Results:</bold> METTL21A was identified as a human protein methyltransferase targeting Hsp70 proteins, thereby altering their ability to interact with client proteins.</p><p><bold>Conclusion:</bold> METTL21A is a specific methyltransferase modulating the function of Hsp70 proteins.</p><p><bold>Significance:</bold> The activity of a human protein-modifying enzyme is unraveled, and the modification is demonstrated to have functional consequences.</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">23921388</article-id><article-id pub-id-type="pmc">3784692</article-id><article-id pub-id-type="publisher-id">M113.483248</article-id><article-id pub-id-type="doi">10.1074/jbc.M113.483248</article-id><article-categories><subj-group subj-group-type="heading"><subject>Enzymology</subject></subj-group></article-categories><title-group><article-title>Identification and Characterization of a Novel Human Methyltransferase Modulating Hsp70 Protein Function through Lysine Methylation<xref ref-type="fn" rid="FN1">*</xref><xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic></sup></xref></article-title><alt-title alt-title-type="short">Characterization of Novel Human Methyltransferase METTL21A</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Jakobsson</surname><given-names>Magnus E.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Moen</surname><given-names>Anders</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bousset</surname><given-names>Luc</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="author-notes" rid="FN3"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Egge-Jacobsen</surname><given-names>Wolfgang</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kernstock</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Melki</surname><given-names>Ronald</given-names></name><xref ref-type="aff" rid="aff2"><sup>§</sup></xref><xref ref-type="author-notes" rid="FN3"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Falnes</surname><given-names>Pål Ø.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo 0316, Norway and</aff><aff id="aff2">the<label>§</label>Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 91198 Gif-sur-Yvette, France</aff></contrib-group><author-notes><corresp id="cor1"><label>2</label> To whom correspondence should be addressed. Tel.: <phone>47-9115-1935</phone>; E-mail: <email>pal.falnes@ibv.uio.no</email>.</corresp><fn fn-type="supported-by" id="FN3"><label>1</label><p>Supported by Agence Nationale pour la Recherche Grant ANR-09-MNPS-013-01, CNRS, the Human Frontier Science Program, and the Fondation Bettencourt Schueller.</p></fn></author-notes><pub-date pub-type="ppub"><day>27</day><month>9</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>6</day><month>8</month><year>2013</year></pub-date><volume>288</volume><issue>39</issue><fpage>27752</fpage><lpage>27763</lpage><history><date date-type="received"><day>6</day><month>5</month><year>2013</year></date><date date-type="rev-recd"><day>21</day><month>6</month><year>2013</year></date></history><permissions><copyright-statement>© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2013</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc03913027752.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> The function of many proteins is regulated through post-translational methylation.</p><p><bold>Results:</bold> METTL21A was identified as a human protein methyltransferase targeting Hsp70 proteins, thereby altering their ability to interact with client proteins.</p><p><bold>Conclusion:</bold> METTL21A is a specific methyltransferase modulating the function of Hsp70 proteins.</p><p><bold>Significance:</bold> The activity of a human protein-modifying enzyme is unraveled, and the modification is demonstrated to have functional consequences.</p></abstract><abstract><p>Hsp70 proteins constitute an evolutionarily conserved protein family of ATP-dependent molecular chaperones involved in a wide range of biological processes. Mammalian Hsp70 proteins are subject to various post-translational modifications, including methylation, but for most of these, a functional role has not been attributed. In this study, we identified the methyltransferase METTL21A as the enzyme responsible for trimethylation of a conserved lysine residue found in several human Hsp70 (HSPA) proteins. This enzyme, denoted by us as <underline>HSPA</underline> lysine (<underline>K</underline>) <underline>m</underline>ethyl<underline>t</underline>ransferase (HSPA-KMT), was found to catalyze trimethylation of various Hsp70 family members both <italic>in vitro</italic> and <italic>in vivo</italic>, and the reaction was stimulated by ATP. Furthermore, we show that HSPA-KMT exclusively methylates 70-kDa proteins in mammalian protein extracts, demonstrating that it is a highly specific enzyme. Finally, we show that trimethylation of HSPA8 (Hsc70) has functional consequences, as it alters the affinity of the chaperone for both the monomeric and fibrillar forms of the Parkinson disease-associated protein α-synuclein.</p></abstract><kwd-group><kwd>Enzyme Catalysis</kwd><kwd>Enzymes</kwd><kwd>Heat Shock Protein</kwd><kwd>Molecular Chaperone</kwd><kwd>Protein Methylation</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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