ParkinsonCanadaV1, PascalFrancis, Curation, bibRecord, 000923

The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability

Identifieur interne : 000923 ( PascalFrancis/Curation ); précédent : 000922; suivant : 000924

The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability

Auteurs : Thomas M. Durcan [Canada] ; Maria Kontogiannea [Canada] ; Thorhildur Thorarinsdottir [Canada] ; Lara Fallon [Canada] ; Aislinn J. Williams [États-Unis] ; Ana Djarmati [États-Unis] ; Tadeu Fantaneanu [Canada] ; Henry L. Paulson [États-Unis] ; Edward A. Fon [Canada]

Source :

Human molecular genetics : (Print) [ 0964-6906 ] ; 2011.

RBID : Pascal:11-0154501

Descripteurs français

Pascal (Inist)
- Mutation, Hérédodégénérescence spinocérébelleuse, Régulation, Gène suppresseur tumeur, Stabilité, Génétique, Maladie de Joseph, Association génétique, Ataxine, Gène Parkin, Ubiquitinylation, Ubiquitination.
Wicri :
- topic : Génétique.

English descriptors

KwdEn :
- Genetics, Joseph disease, Mutation, Regulation(control), Spinocerebellar heredodegeneration, Stability, Tumor suppressor gene, Ubiquitination.

Abstract

Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3. Interestingly, MJD can present clinically with features of Parkinsonism. In this study, we identify parkin, an E3 ubiquitin-ligase responsible for a common familial form of Parkinson's disease, as a novel ataxin-3 binding partner. The interaction between ataxin-3 and parkin is direct, involves multiple domains and is greatly enhanced by parkin self-ubiquitination. Moreover, ataxin-3 deubiquitinates parkin directly in vitro and in cells. Compared with wild-type ataxin-3, MJD-linked polyQ-expanded mutant ataxin-3 is more active, possibly owing to its greater efficiency at DUB K27- and K29-linked Ub conjugates on parkin. Remarkably, mutant but not wild-type ataxin-3 promotes the clearance of parkin via the autophagy pathway. The finding is consistent with the reduction in parkin levels observed in the brains of transgenic mice over-expressing polyQ-expanded but not wild-type ataxin-3, raising the intriguing possibility that increased turnover of parkin may contribute to the pathogenesis of MJD and help explain some of its parkinsonian features.

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A08	`01`	`1`	`ENG`	`@1 The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability`
A11	`01`	`1`		`@1 DURCAN (Thomas M.)`
A11	`02`	`1`		`@1 KONTOGIANNEA (Maria)`
A11	`03`	`1`		`@1 THORARINSDOTTIR (Thorhildur)`
A11	`04`	`1`		`@1 FALLON (Lara)`
A11	`05`	`1`		`@1 WILLIAMS (Aislinn J.)`
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A11	`07`	`1`		`@1 FANTANEANU (Tadeu)`
A11	`08`	`1`		`@1 PAULSON (Henry L.)`
A11	`09`	`1`		`@1 FON (Edward A.)`
A14	`01`			`@1 Centre for Neuronal Survival and McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University @2 Montreal, Quebec, H3A 2B4 @3 CAN @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 4 aut. @Z 7 aut. @Z 9 aut.`
A14	`02`			`@1 Department of Neurology, University of Michigan, 4001 BSRB, 109 Zina Pitcher Place @2 Ann Arbor, MI 48109 @3 USA @Z 5 aut. @Z 6 aut. @Z 8 aut.`
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C01	`01`		`ENG`	@0 Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3. Interestingly, MJD can present clinically with features of Parkinsonism. In this study, we identify parkin, an E3 ubiquitin-ligase responsible for a common familial form of Parkinson's disease, as a novel ataxin-3 binding partner. The interaction between ataxin-3 and parkin is direct, involves multiple domains and is greatly enhanced by parkin self-ubiquitination. Moreover, ataxin-3 deubiquitinates parkin directly in vitro and in cells. Compared with wild-type ataxin-3, MJD-linked polyQ-expanded mutant ataxin-3 is more active, possibly owing to its greater efficiency at DUB K27- and K29-linked Ub conjugates on parkin. Remarkably, mutant but not wild-type ataxin-3 promotes the clearance of parkin via the autophagy pathway. The finding is consistent with the reduction in parkin levels observed in the brains of transgenic mice over-expressing polyQ-expanded but not wild-type ataxin-3, raising the intriguing possibility that increased turnover of parkin may contribute to the pathogenesis of MJD and help explain some of its parkinsonian features.
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Links toward previous steps (curation, corpus...)

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Pascal:11-0154501

Le document en format XML

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<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Centre for Neuronal Survival and McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</s1>
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<series><title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
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<seriesStmt><title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
<idno type="ISSN">0964-6906</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Genetics</term>
<term>Joseph disease</term>
<term>Mutation</term>
<term>Regulation(control)</term>
<term>Spinocerebellar heredodegeneration</term>
<term>Stability</term>
<term>Tumor suppressor gene</term>
<term>Ubiquitination</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Mutation</term>
<term>Hérédodégénérescence spinocérébelleuse</term>
<term>Régulation</term>
<term>Gène suppresseur tumeur</term>
<term>Stabilité</term>
<term>Génétique</term>
<term>Maladie de Joseph</term>
<term>Association génétique</term>
<term>Ataxine</term>
<term>Gène Parkin</term>
<term>Ubiquitinylation</term>
<term>Ubiquitination</term>
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<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term>
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<front><div type="abstract" xml:lang="en">Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3. Interestingly, MJD can present clinically with features of Parkinsonism. In this study, we identify parkin, an E3 ubiquitin-ligase responsible for a common familial form of Parkinson's disease, as a novel ataxin-3 binding partner. The interaction between ataxin-3 and parkin is direct, involves multiple domains and is greatly enhanced by parkin self-ubiquitination. Moreover, ataxin-3 deubiquitinates parkin directly in vitro and in cells. Compared with wild-type ataxin-3, MJD-linked polyQ-expanded mutant ataxin-3 is more active, possibly owing to its greater efficiency at DUB K27- and K29-linked Ub conjugates on parkin. Remarkably, mutant but not wild-type ataxin-3 promotes the clearance of parkin via the autophagy pathway. The finding is consistent with the reduction in parkin levels observed in the brains of transgenic mice over-expressing polyQ-expanded but not wild-type ataxin-3, raising the intriguing possibility that increased turnover of parkin may contribute to the pathogenesis of MJD and help explain some of its parkinsonian features.</div>
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<fA11 i1="01" i2="1"><s1>DURCAN (Thomas M.)</s1>
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<fA11 i1="02" i2="1"><s1>KONTOGIANNEA (Maria)</s1>
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<fA11 i1="09" i2="1"><s1>FON (Edward A.)</s1>
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<fA14 i1="01"><s1>Centre for Neuronal Survival and McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University</s1>
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<fA14 i1="02"><s1>Department of Neurology, University of Michigan, 4001 BSRB, 109 Zina Pitcher Place</s1>
<s2>Ann Arbor, MI 48109</s2>
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<fC01 i1="01" l="ENG"><s0>Machado-Joseph disease (MJD), the most common dominantly inherited ataxia worldwide, is caused by a polyglutamine (polyQ) expansion in the deubiquitinating (DUB) enzyme ataxin-3. Interestingly, MJD can present clinically with features of Parkinsonism. In this study, we identify parkin, an E3 ubiquitin-ligase responsible for a common familial form of Parkinson's disease, as a novel ataxin-3 binding partner. The interaction between ataxin-3 and parkin is direct, involves multiple domains and is greatly enhanced by parkin self-ubiquitination. Moreover, ataxin-3 deubiquitinates parkin directly in vitro and in cells. Compared with wild-type ataxin-3, MJD-linked polyQ-expanded mutant ataxin-3 is more active, possibly owing to its greater efficiency at DUB K27- and K29-linked Ub conjugates on parkin. Remarkably, mutant but not wild-type ataxin-3 promotes the clearance of parkin via the autophagy pathway. The finding is consistent with the reduction in parkin levels observed in the brains of transgenic mice over-expressing polyQ-expanded but not wild-type ataxin-3, raising the intriguing possibility that increased turnover of parkin may contribute to the pathogenesis of MJD and help explain some of its parkinsonian features.</s0>
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	La maladie de Parkinson au Canada (serveur d'exploration)
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La maladie de Parkinson au Canada (serveur d'exploration)

The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability

The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability

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