The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes
Identifieur interne : 001C51 ( Main/Corpus ); précédent : 001C50; suivant : 001C52The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes
Auteurs : Maria G. Macedo ; Burcu Anar ; Iraad F. Bronner ; Milena Cannella ; Ferdinando Squitieri ; Vincenzo Bonifati ; Andre Hoogeveen ; Peter Heutink ; Patrizia RizzuSource :
- Human Molecular Genetics [ 0964-6906 ] ; 2003-11-01.
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently DJ-1 mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1L166P mutant protein shows a different elution profile as compared with DJ-1WT both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1L166P mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT–PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. This rapid turnover and the structural changes of DJ-1L166P mutant protein might be crucial in the disease pathogenesis.
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DOI: 10.1093/hmg/ddg304
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Macedo</name><affiliation><mods:affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author><author><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><affiliation><mods:affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author><author><name sortKey="Bronner, Iraad F" sort="Bronner, Iraad F" uniqKey="Bronner I" first="Iraad F." last="Bronner">Iraad F. 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Macedo</name><affiliation><mods:affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author><author><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><affiliation><mods:affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author><author><name sortKey="Bronner, Iraad F" sort="Bronner, Iraad F" uniqKey="Bronner I" first="Iraad F." last="Bronner">Iraad F. Bronner</name><affiliation><mods:affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author><author><name sortKey="Cannella, Milena" sort="Cannella, Milena" uniqKey="Cannella M" first="Milena" last="Cannella">Milena Cannella</name><affiliation><mods:affiliation>Neurogenetics Unit, IRCCS Neuromed, 86077, Pozzilli, Italy and</mods:affiliation></affiliation></author><author><name sortKey="Squitieri, Ferdinando" sort="Squitieri, Ferdinando" uniqKey="Squitieri F" first="Ferdinando" last="Squitieri">Ferdinando Squitieri</name><affiliation><mods:affiliation>Neurogenetics Unit, IRCCS Neuromed, 86077, Pozzilli, Italy and</mods:affiliation></affiliation></author><author><name sortKey="Bonifati, Vincenzo" sort="Bonifati, Vincenzo" uniqKey="Bonifati V" first="Vincenzo" last="Bonifati">Vincenzo Bonifati</name><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Neurological Sciences, La Sapienza University, 00185 Rome, Italy</mods:affiliation></affiliation></author><author><name sortKey="Hoogeveen, Andre" sort="Hoogeveen, Andre" uniqKey="Hoogeveen A" first="Andre" last="Hoogeveen">Andre Hoogeveen</name><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author><author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><affiliation><mods:affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author><author><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name><affiliation><mods:affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Molecular Genetics</title><title level="j" type="abbrev">Hum. Mol. Genet.</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2003-11-01">2003-11-01</date><biblScope unit="volume">12</biblScope><biblScope unit="issue">21</biblScope><biblScope unit="page" from="2807">2807</biblScope><biblScope unit="page" to="2816">2816</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">8D44553C5F72BDD2D94AB1C5A593CA95AD295978</idno><idno type="DOI">10.1093/hmg/ddg304</idno><idno type="local">ddg304</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently DJ-1 mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1L166P mutant protein shows a different elution profile as compared with DJ-1WT both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1L166P mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT–PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. This rapid turnover and the structural changes of DJ-1L166P mutant protein might be crucial in the disease pathogenesis.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Maria G. Macedo</name><affiliations><json:string>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</json:string><json:string>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</json:string></affiliations></json:item><json:item><name>Burcu Anar</name><affiliations><json:string>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</json:string><json:string>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</json:string></affiliations></json:item><json:item><name>Iraad F. Bronner</name><affiliations><json:string>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</json:string><json:string>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</json:string></affiliations></json:item><json:item><name>Milena Cannella</name><affiliations><json:string>Neurogenetics Unit, IRCCS Neuromed, 86077, Pozzilli, Italy and</json:string></affiliations></json:item><json:item><name>Ferdinando Squitieri</name><affiliations><json:string>Neurogenetics Unit, IRCCS Neuromed, 86077, Pozzilli, Italy and</json:string></affiliations></json:item><json:item><name>Vincenzo Bonifati</name><affiliations><json:string>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</json:string><json:string>Department of Neurological Sciences, La Sapienza University, 00185 Rome, Italy</json:string></affiliations></json:item><json:item><name>André Hoogeveen</name><affiliations><json:string>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</json:string></affiliations></json:item><json:item><name>Peter Heutink</name><affiliations><json:string>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</json:string><json:string>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</json:string></affiliations></json:item><json:item><name>Patrizia Rizzu</name><affiliations><json:string>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</json:string><json:string>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Article</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently DJ-1 mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1L166P mutant protein shows a different elution profile as compared with DJ-1WT both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1L166P mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT–PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. 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Mol. Genet.</title><idno type="pISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2003-11-01"></date><biblScope unit="volume">12</biblScope><biblScope unit="issue">21</biblScope><biblScope unit="page" from="2807">2807</biblScope><biblScope unit="page" to="2816">2816</biblScope></imprint></monogr><idno type="istex">8D44553C5F72BDD2D94AB1C5A593CA95AD295978</idno><idno type="DOI">10.1093/hmg/ddg304</idno><idno type="local">ddg304</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2003</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently DJ-1 mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1L166P mutant protein shows a different elution profile as compared with DJ-1WT both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1L166P mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT–PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. This rapid turnover and the structural changes of DJ-1L166P mutant protein might be crucial in the disease pathogenesis.</p></abstract></profileDesc><revisionDesc><change when="2003-11-01">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-3-15">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/8D44553C5F72BDD2D94AB1C5A593CA95AD295978/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="US-ASCII"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article xml:lang="en" article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">hmg</journal-id><journal-id journal-id-type="nlm-ta">Hum Mol Genet</journal-id><journal-id journal-id-type="publisher-id">hmg</journal-id><journal-title>Human Molecular Genetics</journal-title><abbrev-journal-title abbrev-type="publisher">Hum. Mol. Genet.</abbrev-journal-title><issn pub-type="ppub">0964-6906</issn><issn pub-type="epub">1460-2083</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="other">ddg304</article-id><article-id pub-id-type="doi">10.1093/hmg/ddg304</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>The DJ-1<sup>L166P</sup> mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Macedo</surname><given-names>Maria G.</given-names></name><xref rid="AF1">1</xref><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Anar</surname><given-names>Burcu</given-names></name><xref rid="AF1">1</xref><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bronner</surname><given-names>Iraad F.</given-names></name><xref rid="AF1">1</xref><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Cannella</surname><given-names>Milena</given-names></name><xref rid="AF3">3</xref></contrib><contrib contrib-type="author"><name><surname>Squitieri</surname><given-names>Ferdinando</given-names></name><xref rid="AF3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bonifati</surname><given-names>Vincenzo</given-names></name><xref rid="AF2">2</xref><xref rid="AF4">4</xref></contrib><contrib contrib-type="author"><name><surname>Hoogeveen</surname><given-names>André</given-names></name><xref rid="AF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Heutink</surname><given-names>Peter</given-names></name><xref rid="AF1">1</xref><xref rid="AF2">2</xref><xref rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Rizzu</surname><given-names>Patrizia</given-names></name><xref rid="AF1">1</xref><xref rid="AF2">2</xref></contrib><aff id="AF1"><sup>1</sup>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</aff><aff id="AF2"><sup>2</sup>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</aff><aff id="AF3"><sup>3</sup>Neurogenetics Unit, IRCCS Neuromed, 86077, Pozzilli, Italy and</aff><aff id="AF4"><sup>4</sup>Department of Neurological Sciences, La Sapienza University, 00185 Rome, Italy</aff></contrib-group><pub-date pub-type="ppub"><day>1</day><month>11</month><year>2003</year></pub-date><volume>12</volume><issue>21</issue><fpage>2807</fpage><lpage>2816</lpage><history><date date-type="accepted"><day>27</day><month>08</month><year>2003</year></date><date date-type="received"><day>29</day><month>06</month><year>2003</year></date></history><permissions><copyright-year>2003</copyright-year></permissions><abstract xml:lang="en"><p>Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently <italic>DJ-1</italic> mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1<sup>L166P</sup> mutant protein shows a different elution profile as compared with DJ-1<sup>WT</sup> both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1<sup>L166P</sup> mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT–PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. This rapid turnover and the structural changes of DJ-1<sup>L166P</sup> mutant protein might be crucial in the disease pathogenesis.</p></abstract><custom-meta-wrap><custom-meta><meta-name>hwp-legacy-fpage</meta-name><meta-value>2807</meta-value></custom-meta><custom-meta><meta-name>hwp-legacy-dochead</meta-name><meta-value>Article</meta-value></custom-meta></custom-meta-wrap></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes</title></titleInfo><name type="personal"><namePart type="given">Maria G.</namePart><namePart type="family">Macedo</namePart><affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</affiliation><affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Burcu</namePart><namePart type="family">Anar</namePart><affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</affiliation><affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Iraad F.</namePart><namePart type="family">Bronner</namePart><affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</affiliation><affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Milena</namePart><namePart type="family">Cannella</namePart><affiliation>Neurogenetics Unit, IRCCS Neuromed, 86077, Pozzilli, Italy and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ferdinando</namePart><namePart type="family">Squitieri</namePart><affiliation>Neurogenetics Unit, IRCCS Neuromed, 86077, Pozzilli, Italy and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vincenzo</namePart><namePart type="family">Bonifati</namePart><affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</affiliation><affiliation>Department of Neurological Sciences, La Sapienza University, 00185 Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">André</namePart><namePart type="family">Hoogeveen</namePart><affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter</namePart><namePart type="family">Heutink</namePart><affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</affiliation><affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrizia</namePart><namePart type="family">Rizzu</namePart><affiliation>Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, 1081 BT Amsterdam, The Netherlands,</affiliation><affiliation>Department of Clinical Genetics, ErasmusMC, 3000 DR Rotterdam, The Netherlands,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2003-11-01</dateIssued><copyrightDate encoding="w3cdtf">2003</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Parkinson's disease (PD) is a common neurodegenerative disorder that involves the selective degeneration of midbrain dopaminergic neurons. Recently DJ-1 mutations have been linked to autosomal-recessive early-onset Parkinsonism in two European families. By using gel filtration assays under physiological conditions we demonstrate that DJ-1 protein forms a dimeric structure. Conversely, the DJ-1L166P mutant protein shows a different elution profile as compared with DJ-1WT both in overexpression cellular systems or in lymphoblasts cells, suggesting that it might form higher order protein structures. Furthermore we observed that the level of DJ-1L166P mutant protein in the patient's lymphoblasts was very low as compared with the wild-type protein. We excluded a potential transcriptional impairment by performing quantitative RT–PCR on the patient's material. Pulse-chase experiments in transfected COS-1 cells and cycloheximide treatment in control and patient lymphoblasts indicated that the mutant protein was rapidly degraded. This rapid turnover and the structural changes of DJ-1L166P mutant protein might be crucial in the disease pathogenesis.</abstract><relatedItem type="host"><titleInfo><title>Human Molecular Genetics</title></titleInfo><titleInfo type="abbreviated"><title>Hum. Mol. Genet.</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0964-6906</identifier><identifier type="eISSN">1460-2083</identifier><identifier type="PublisherID">hmg</identifier><identifier type="PublisherID-hwp">hmg</identifier><identifier type="PublisherID-nlm-ta">Hum Mol Genet</identifier><part><date>2003</date><detail type="volume"><caption>vol.</caption><number>12</number></detail><detail type="issue"><caption>no.</caption><number>21</number></detail><extent unit="pages"><start>2807</start><end>2816</end></extent></part></relatedItem><identifier type="istex">8D44553C5F72BDD2D94AB1C5A593CA95AD295978</identifier><identifier type="DOI">10.1093/hmg/ddg304</identifier><identifier type="local">ddg304</identifier><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/8D44553C5F72BDD2D94AB1C5A593CA95AD295978/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/8D44553C5F72BDD2D94AB1C5A593CA95AD295978/annexes/gif</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/8D44553C5F72BDD2D94AB1C5A593CA95AD295978/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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