The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes
Identifieur interne : 001700 ( Main/Exploration ); précédent : 001699; suivant : 001701The 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 [Italie] ; 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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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><affiliations><list><country><li>Italie</li></country><region><li>Latium</li></region><settlement><li>Rome</li></settlement></list><tree><noCountry><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><name sortKey="Bronner, Iraad F" sort="Bronner, Iraad F" uniqKey="Bronner I" first="Iraad F." last="Bronner">Iraad F. Bronner</name><name sortKey="Cannella, Milena" sort="Cannella, Milena" uniqKey="Cannella M" first="Milena" last="Cannella">Milena Cannella</name><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><name sortKey="Hoogeveen, Andre" sort="Hoogeveen, Andre" uniqKey="Hoogeveen A" first="Andre" last="Hoogeveen">Andre Hoogeveen</name><name sortKey="Macedo, Maria G" sort="Macedo, Maria G" uniqKey="Macedo M" first="Maria G." last="Macedo">Maria G. Macedo</name><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name><name sortKey="Squitieri, Ferdinando" sort="Squitieri, Ferdinando" uniqKey="Squitieri F" first="Ferdinando" last="Squitieri">Ferdinando Squitieri</name></noCountry><country name="Italie"><region name="Latium"><name sortKey="Bonifati, Vincenzo" sort="Bonifati, Vincenzo" uniqKey="Bonifati V" first="Vincenzo" last="Bonifati">Vincenzo Bonifati</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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