Choice of Biological Source Material Supersedes Oxidative Stress in Its Influence on DJ-1 in Vivo Interactions with Hsp90
Identifieur interne : 001706 ( Main/Exploration ); précédent : 001705; suivant : 001707Choice of Biological Source Material Supersedes Oxidative Stress in Its Influence on DJ-1 in Vivo Interactions with Hsp90
Auteurs : Christiane B. Knobbe [Canada] ; Timothy J. Revett [Canada] ; Yu Bai [Canada] ; Vinca Chow [Canada] ; Amy Hye Won Jeon [Canada] ; Christopher Böhm [Canada] ; Sepehr Ehsani [Canada] ; Thomas Kislinger [Canada] ; Howard T. Mount [Canada] ; Tak W. Mak [Canada] ; Peter St. George-Hyslop [Canada, Royaume-Uni] ; Gerold Schmitt-Ulms [Canada]Source :
- Journal of proteome research [ 1535-3893 ] ; 2011.
Abstract
DJ-1 is a small but relatively abundant protein of unknown function that may undergo stress-dependent cellular translocation and has been implicated in both neurodegenerative diseases and cancer. As such, DJ-1 may be an excellent study object to elucidate the relative influence of the cellular context on its interactome and for exploring whether acute exposure to oxidative stressors alters its molecular environment. Using quantitative mass spectrometry, we conducted comparative DJ-1 interactome analyses from in vivo cross-linked brains or livers and from hydrogen peroxide-treated or naïve embryonic stem cells. The analysis identified a subset of glycolytic enzymes, heat shock proteins 70 and 90, and peroxiredoxins as interactors of DJ-1. Consistent with a role of DJ-1 in Hsp90 chaperone biology, we document destabilization of Hsp90 clients in DJ-1 knockout cells. We further demonstrate the existence of a C106 sulfinic acid modification within DJ-1 and thereby establish that this previously inferred modification also exists in vivo. Our data suggest that caution has to be exerted in interpreting interactome data obtained from a single biological source material and identify a role of DJ-1 as an oxidative stress sensor and partner of a molecular machinery notorious for its involvement in cell fate decisions.
Url:
DOI: 10.1021/pr200225c
PubMed: 21819105
PubMed Central: 5006933
Affiliations:
- Canada, Royaume-Uni
- Angleterre, Angleterre de l'Est, Ontario
- Cambridge, Toronto
- Université de Cambridge, Université de Toronto
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Knobbe</name><affiliation wicri:level="1"><nlm:aff id="A1">Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C1</wicri:regionArea><wicri:noRegion>Ontario M5G 2C1</wicri:noRegion></affiliation></author><author><name sortKey="Revett, Timothy J" sort="Revett, Timothy J" uniqKey="Revett T" first="Timothy J." last="Revett">Timothy J. Revett</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Bai, Yu" sort="Bai, Yu" uniqKey="Bai Y" first="Yu" last="Bai">Yu Bai</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Chow, Vinca" sort="Chow, Vinca" uniqKey="Chow V" first="Vinca" last="Chow">Vinca Chow</name><affiliation wicri:level="1"><nlm:aff id="A1">Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C1</wicri:regionArea><wicri:noRegion>Ontario M5G 2C1</wicri:noRegion></affiliation></author><author><name sortKey="Jeon, Amy Hye Won" sort="Jeon, Amy Hye Won" uniqKey="Jeon A" first="Amy Hye Won" last="Jeon">Amy Hye Won Jeon</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Bohm, Christopher" sort="Bohm, Christopher" uniqKey="Bohm C" first="Christopher" last="Böhm">Christopher Böhm</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Ehsani, Sepehr" sort="Ehsani, Sepehr" uniqKey="Ehsani S" first="Sepehr" last="Ehsani">Sepehr Ehsani</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Kislinger, Thomas" sort="Kislinger, Thomas" uniqKey="Kislinger T" first="Thomas" last="Kislinger">Thomas Kislinger</name><affiliation wicri:level="1"><nlm:aff id="A3">Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, University Health Network, Toronto Medical Discovery Tower, Toronto, Ontario M5G 1L7, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, University Health Network, Toronto Medical Discovery Tower, Toronto, Ontario M5G 1L7</wicri:regionArea><wicri:noRegion>Ontario M5G 1L7</wicri:noRegion></affiliation></author><author><name sortKey="Mount, Howard T" sort="Mount, Howard T" uniqKey="Mount H" first="Howard T." last="Mount">Howard T. Mount</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><affiliation wicri:level="1"><nlm:aff id="A1">Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C1, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 2C1</wicri:regionArea><wicri:noRegion>Ontario M5G 2C1</wicri:noRegion></affiliation></author><author><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St. George-Hyslop">Peter St. George-Hyslop</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="A4">Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, U.K</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Schmitt Ulms, Gerold" sort="Schmitt Ulms, Gerold" uniqKey="Schmitt Ulms G" first="Gerold" last="Schmitt-Ulms">Gerold Schmitt-Ulms</name><affiliation wicri:level="4"><nlm:aff id="A2">Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Laboratory Medicine and Pathobiology, Medical Biophysics, and Medicine (Neurology), Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">Journal of proteome research</title><idno type="ISSN">1535-3893</idno><idno type="eISSN">1535-3907</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P3">DJ-1 is a small but relatively abundant protein of unknown function that may undergo stress-dependent cellular translocation and has been implicated in both neurodegenerative diseases and cancer. As such, DJ-1 may be an excellent study object to elucidate the relative influence of the cellular context on its interactome and for exploring whether acute exposure to oxidative stressors alters its molecular environment. Using quantitative mass spectrometry, we conducted comparative DJ-1 interactome analyses from in vivo cross-linked brains or livers and from hydrogen peroxide-treated or naïve embryonic stem cells. The analysis identified a subset of glycolytic enzymes, heat shock proteins 70 and 90, and peroxiredoxins as interactors of DJ-1. Consistent with a role of DJ-1 in Hsp90 chaperone biology, we document destabilization of Hsp90 clients in DJ-1 knockout cells. We further demonstrate the existence of a C106 sulfinic acid modification within DJ-1 and thereby establish that this previously inferred modification also exists in vivo. Our data suggest that caution has to be exerted in interpreting interactome data obtained from a single biological source material and identify a role of DJ-1 as an oxidative stress sensor and partner of a molecular machinery notorious for its involvement in cell fate decisions.</p></div></front></TEI><affiliations><list><country><li>Canada</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Ontario</li></region><settlement><li>Cambridge</li><li>Toronto</li></settlement><orgName><li>Université de Cambridge</li><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Knobbe, Christiane B" sort="Knobbe, Christiane B" uniqKey="Knobbe C" first="Christiane B." last="Knobbe">Christiane B. Knobbe</name></noRegion><name sortKey="Bai, Yu" sort="Bai, Yu" uniqKey="Bai Y" first="Yu" last="Bai">Yu Bai</name><name sortKey="Bohm, Christopher" sort="Bohm, Christopher" uniqKey="Bohm C" first="Christopher" last="Böhm">Christopher Böhm</name><name sortKey="Chow, Vinca" sort="Chow, Vinca" uniqKey="Chow V" first="Vinca" last="Chow">Vinca Chow</name><name sortKey="Ehsani, Sepehr" sort="Ehsani, Sepehr" uniqKey="Ehsani S" first="Sepehr" last="Ehsani">Sepehr Ehsani</name><name sortKey="Jeon, Amy Hye Won" sort="Jeon, Amy Hye Won" uniqKey="Jeon A" first="Amy Hye Won" last="Jeon">Amy Hye Won Jeon</name><name sortKey="Kislinger, Thomas" sort="Kislinger, Thomas" uniqKey="Kislinger T" first="Thomas" last="Kislinger">Thomas Kislinger</name><name sortKey="Mak, Tak W" sort="Mak, Tak W" uniqKey="Mak T" first="Tak W." last="Mak">Tak W. Mak</name><name sortKey="Mount, Howard T" sort="Mount, Howard T" uniqKey="Mount H" first="Howard T." last="Mount">Howard T. Mount</name><name sortKey="Revett, Timothy J" sort="Revett, Timothy J" uniqKey="Revett T" first="Timothy J." last="Revett">Timothy J. Revett</name><name sortKey="Schmitt Ulms, Gerold" sort="Schmitt Ulms, Gerold" uniqKey="Schmitt Ulms G" first="Gerold" last="Schmitt-Ulms">Gerold Schmitt-Ulms</name><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St. George-Hyslop">Peter St. George-Hyslop</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="St George Hyslop, Peter" sort="St George Hyslop, Peter" uniqKey="St George Hyslop P" first="Peter" last="St. George-Hyslop">Peter St. George-Hyslop</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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