Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function
Identifieur interne : 000980 ( Main/Exploration ); précédent : 000979; suivant : 000981Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function
Auteurs : Eleanor J. Davison [Royaume-Uni] ; Kyla Pennington [Royaume-Uni] ; Chao-Chun Hung [Royaume-Uni] ; Jianhe Peng [Royaume-Uni] ; Rumana Rafiq [Royaume-Uni] ; Antje Ostareck-Lederer [Allemagne] ; Dirk H. Ostareck [Allemagne] ; Helen C. Ardley [Royaume-Uni] ; Rosamonde E. Banks [Royaume-Uni] ; Philip A. Robinson [Royaume-Uni]Source :
- PROTEOMICS [ 1615-9853 ] ; 2009-09.
English descriptors
- KwdEn :
Abstract
Parkin is an ubiquitin‐protein ligase (E3), mutations of which cause juvenile onset – autosomal recessive Parkinson's disease, and result in reduced enzymic activity. In contrast, increased levels are protective against mitochondrial dysfunction and neurodegeneration, the mechanism of which is largely unknown. In this study, 2‐DE and MS proteomic techniques were utilised to investigate the effects of increased Parkin levels on protein expression in whole cell lysates using in an inducible Parkin expression system in HEK293 cells, and also to isolate potential interactants of Parkin using tandem affinity purification and MS. Nine proteins were significantly differentially expressed (±2‐fold change; p<0.05) using 2‐DE analysis. MS revealed the identity of these proteins to be ACAT2, HNRNPK, HSPD1, PGK1, PRDX6, VCL, VIM, TPI1, and IMPDH2. The first seven of these were reduced in expression. Western blot analysis confirmed the reduction in one of these proteins (HNRNPK), and that its levels were dependent on 26S proteasomal activity. Tandem affinity purification/MS revealed 14 potential interactants of Parkin; CKB, DBT, HSPD1, HSPA9, LRPPRC, NDUFS2, PRDX6, SLC25A5, TPI1, UCHL1, UQCRC1, VCL, YWHAZ, YWHAE. Nine of these are directly involved in mitochondrial energy metabolism and glycolysis; four were also identified in the 2‐DE study (HSP60, PRDX6, TPI1, and VCL). This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells.
Url:
DOI: 10.1002/pmic.200900126
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function</title><author><name sortKey="Davison, Eleanor J" sort="Davison, Eleanor J" uniqKey="Davison E" first="Eleanor J." last="Davison">Eleanor J. Davison</name></author><author><name sortKey="Pennington, Kyla" sort="Pennington, Kyla" uniqKey="Pennington K" first="Kyla" last="Pennington">Kyla Pennington</name></author><author><name sortKey="Hung, Chao Hun" sort="Hung, Chao Hun" uniqKey="Hung C" first="Chao-Chun" last="Hung">Chao-Chun Hung</name></author><author><name sortKey="Peng, Jianhe" sort="Peng, Jianhe" uniqKey="Peng J" first="Jianhe" last="Peng">Jianhe Peng</name></author><author><name sortKey="Rafiq, Rumana" sort="Rafiq, Rumana" uniqKey="Rafiq R" first="Rumana" last="Rafiq">Rumana Rafiq</name></author><author><name sortKey="Ostareck Ederer, Antje" sort="Ostareck Ederer, Antje" uniqKey="Ostareck Ederer A" first="Antje" last="Ostareck-Lederer">Antje Ostareck-Lederer</name></author><author><name sortKey="Ostareck, Dirk H" sort="Ostareck, Dirk H" uniqKey="Ostareck D" first="Dirk H." last="Ostareck">Dirk H. Ostareck</name></author><author><name sortKey="Ardley, Helen C" sort="Ardley, Helen C" uniqKey="Ardley H" first="Helen C." last="Ardley">Helen C. Ardley</name></author><author><name sortKey="Banks, Rosamonde E" sort="Banks, Rosamonde E" uniqKey="Banks R" first="Rosamonde E." last="Banks">Rosamonde E. Banks</name></author><author><name sortKey="Robinson, Philip A" sort="Robinson, Philip A" uniqKey="Robinson P" first="Philip A." last="Robinson">Philip A. Robinson</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:6AC3E8E51F8BECE57E297380184825D3434DDD6E</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1002/pmic.200900126</idno><idno type="url">https://api.istex.fr/document/6AC3E8E51F8BECE57E297380184825D3434DDD6E/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002500</idno><idno type="wicri:Area/Main/Curation">002170</idno><idno type="wicri:Area/Main/Exploration">000980</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function</title><author><name sortKey="Davison, Eleanor J" sort="Davison, Eleanor J" uniqKey="Davison E" first="Eleanor J." last="Davison">Eleanor J. Davison</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Section of Ophthalmology and Neuroscience, Leeds Institute for Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Pennington, Kyla" sort="Pennington, Kyla" uniqKey="Pennington K" first="Kyla" last="Pennington">Kyla Pennington</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Section of Ophthalmology and Neuroscience, Leeds Institute for Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Hung, Chao Hun" sort="Hung, Chao Hun" uniqKey="Hung C" first="Chao-Chun" last="Hung">Chao-Chun Hung</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Section of Ophthalmology and Neuroscience, Leeds Institute for Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Peng, Jianhe" sort="Peng, Jianhe" uniqKey="Peng J" first="Jianhe" last="Peng">Jianhe Peng</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Clinical Centre, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Rafiq, Rumana" sort="Rafiq, Rumana" uniqKey="Rafiq R" first="Rumana" last="Rafiq">Rumana Rafiq</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Clinical Centre, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Ostareck Ederer, Antje" sort="Ostareck Ederer, Antje" uniqKey="Ostareck Ederer A" first="Antje" last="Ostareck-Lederer">Antje Ostareck-Lederer</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biochemistry, Martin‐Luther University Halle‐Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author><author><name sortKey="Ostareck, Dirk H" sort="Ostareck, Dirk H" uniqKey="Ostareck D" first="Dirk H." last="Ostareck">Dirk H. Ostareck</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biochemistry, Martin‐Luther University Halle‐Wittenberg, Halle (Saale)</wicri:regionArea><wicri:noRegion>Halle (Saale)</wicri:noRegion><wicri:noRegion>Halle (Saale)</wicri:noRegion></affiliation></author><author><name sortKey="Ardley, Helen C" sort="Ardley, Helen C" uniqKey="Ardley H" first="Helen C." last="Ardley">Helen C. Ardley</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Section of Ophthalmology and Neuroscience, Leeds Institute for Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Banks, Rosamonde E" sort="Banks, Rosamonde E" uniqKey="Banks R" first="Rosamonde E." last="Banks">Rosamonde E. Banks</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cancer Research UK Clinical Centre, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author><author><name sortKey="Robinson, Philip A" sort="Robinson, Philip A" uniqKey="Robinson P" first="Philip A." last="Robinson">Philip A. Robinson</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Section of Ophthalmology and Neuroscience, Leeds Institute for Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">PROTEOMICS</title><title level="j" type="abbrev">Proteomics</title><idno type="ISSN">1615-9853</idno><idno type="eISSN">1615-9861</idno><imprint><publisher>WILEY‐VCH Verlag</publisher><pubPlace>Weinheim</pubPlace><date type="published" when="2009-09">2009-09</date><biblScope unit="volume">9</biblScope><biblScope unit="issue">18</biblScope><biblScope unit="page" from="4284">4284</biblScope><biblScope unit="page" to="4297">4297</biblScope></imprint><idno type="ISSN">1615-9853</idno></series><idno type="istex">6AC3E8E51F8BECE57E297380184825D3434DDD6E</idno><idno type="DOI">10.1002/pmic.200900126</idno><idno type="ArticleID">PMIC200900126</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1615-9853</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>2‐DE</term><term>Cell biology</term><term>Mitochondria</term><term>Parkin</term><term>Parkinson's disease</term><term>Ubiquitination</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkin is an ubiquitin‐protein ligase (E3), mutations of which cause juvenile onset – autosomal recessive Parkinson's disease, and result in reduced enzymic activity. In contrast, increased levels are protective against mitochondrial dysfunction and neurodegeneration, the mechanism of which is largely unknown. In this study, 2‐DE and MS proteomic techniques were utilised to investigate the effects of increased Parkin levels on protein expression in whole cell lysates using in an inducible Parkin expression system in HEK293 cells, and also to isolate potential interactants of Parkin using tandem affinity purification and MS. Nine proteins were significantly differentially expressed (±2‐fold change; p<0.05) using 2‐DE analysis. MS revealed the identity of these proteins to be ACAT2, HNRNPK, HSPD1, PGK1, PRDX6, VCL, VIM, TPI1, and IMPDH2. The first seven of these were reduced in expression. Western blot analysis confirmed the reduction in one of these proteins (HNRNPK), and that its levels were dependent on 26S proteasomal activity. Tandem affinity purification/MS revealed 14 potential interactants of Parkin; CKB, DBT, HSPD1, HSPA9, LRPPRC, NDUFS2, PRDX6, SLC25A5, TPI1, UCHL1, UQCRC1, VCL, YWHAZ, YWHAE. Nine of these are directly involved in mitochondrial energy metabolism and glycolysis; four were also identified in the 2‐DE study (HSP60, PRDX6, TPI1, and VCL). This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Davison, Eleanor J" sort="Davison, Eleanor J" uniqKey="Davison E" first="Eleanor J." last="Davison">Eleanor J. Davison</name></noRegion><name sortKey="Ardley, Helen C" sort="Ardley, Helen C" uniqKey="Ardley H" first="Helen C." last="Ardley">Helen C. Ardley</name><name sortKey="Banks, Rosamonde E" sort="Banks, Rosamonde E" uniqKey="Banks R" first="Rosamonde E." last="Banks">Rosamonde E. Banks</name><name sortKey="Hung, Chao Hun" sort="Hung, Chao Hun" uniqKey="Hung C" first="Chao-Chun" last="Hung">Chao-Chun Hung</name><name sortKey="Peng, Jianhe" sort="Peng, Jianhe" uniqKey="Peng J" first="Jianhe" last="Peng">Jianhe Peng</name><name sortKey="Pennington, Kyla" sort="Pennington, Kyla" uniqKey="Pennington K" first="Kyla" last="Pennington">Kyla Pennington</name><name sortKey="Rafiq, Rumana" sort="Rafiq, Rumana" uniqKey="Rafiq R" first="Rumana" last="Rafiq">Rumana Rafiq</name><name sortKey="Robinson, Philip A" sort="Robinson, Philip A" uniqKey="Robinson P" first="Philip A." last="Robinson">Philip A. Robinson</name></country><country name="Allemagne"><noRegion><name sortKey="Ostareck Ederer, Antje" sort="Ostareck Ederer, Antje" uniqKey="Ostareck Ederer A" first="Antje" last="Ostareck-Lederer">Antje Ostareck-Lederer</name></noRegion><name sortKey="Ostareck, Dirk H" sort="Ostareck, Dirk H" uniqKey="Ostareck D" first="Dirk H." last="Ostareck">Dirk H. Ostareck</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000980 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000980 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:6AC3E8E51F8BECE57E297380184825D3434DDD6E
|texte= Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function
}}
| This area was generated with Dilib version V0.6.23. |  |