ER-stress-associated functional link between Parkin and DJ-1 via a transcriptional cascade involving the tumor suppressor p53 and the spliced X-box binding protein XBP-1.
Identifieur interne : 000D34 ( Main/Exploration ); précédent : 000D33; suivant : 000D35ER-stress-associated functional link between Parkin and DJ-1 via a transcriptional cascade involving the tumor suppressor p53 and the spliced X-box binding protein XBP-1.
Auteurs : Eric Duplan [France] ; Emilie Giaime ; Julien Viotti ; Jean Sévalle ; Olga Corti ; Alexis Brice ; Hiroyoshi Ariga ; Ling Qi ; Frédéric Checler ; Cristine Alves Da CostaSource :
- Journal of cell science [ 1477-9137 ] ; 2013.
English descriptors
- KwdEn :
- Animals, Cell Line, Tumor, DNA-Binding Proteins (genetics), DNA-Binding Proteins (metabolism), Endoplasmic Reticulum Stress, Gene Expression Regulation (genetics), HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins (genetics), Intracellular Signaling Peptides and Proteins (metabolism), Mice, Mice, Mutant Strains (genetics), Oncogene Proteins (genetics), Oncogene Proteins (metabolism), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (pathology), Peroxiredoxins, Protein Deglycase DJ-1, Regulatory Factor X Transcription Factors, Signal Transduction (genetics), Transcription Factors (genetics), Transcription Factors (metabolism), Transcription, Genetic, Tumor Suppressor Protein p53 (genetics), Tumor Suppressor Protein p53 (metabolism), Ubiquitin-Protein Ligases (genetics), Ubiquitin-Protein Ligases (metabolism), X-Box Binding Protein 1.
- MESH :
- chemical , genetics : DNA-Binding Proteins, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Transcription Factors, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases.
- chemical , metabolism : DNA-Binding Proteins, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Transcription Factors, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases.
- genetics : Gene Expression Regulation, Mice, Mutant Strains, Parkinson Disease, Signal Transduction.
- metabolism : Parkinson Disease.
- pathology : Parkinson Disease.
- Animals, Cell Line, Tumor, Endoplasmic Reticulum Stress, HEK293 Cells, Humans, Mice, Peroxiredoxins, Protein Deglycase DJ-1, Regulatory Factor X Transcription Factors, Transcription, Genetic, X-Box Binding Protein 1.
Abstract
Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinson's disease (PD) that have been shown to functionally interact by as-yet-unknown mechanisms. We have delineated the mechanisms by which parkin controls DJ-1. Parkin modulates DJ-1 transcription and protein levels via a signaling cascade involving p53 and the endoplasmic reticulum (ER)-stress-induced active X-box-binding protein-1S (XBP-1S). Parkin triggers the transcriptional repression of p53 while p53 downregulates DJ-1 protein and mRNA expressions. We show that parkin-mediated control of DJ-1 is fully p53-dependent. Furthermore, we establish that p53 lowers the protein and mRNA levels of XBP-1S. Accordingly, we show that parkin ultimately upregulates XBP-1 levels. Subsequently, XBP-1S physically interacts with the DJ-1 promoter, thereby enhancing its promoter trans-activation, mRNA levels and protein expression. This data was corroborated by the examination of DJ-1 in both parkin- and p53-null mice brains. This transcriptional cascade is abolished by pathogenic parkin mutations and is independent of its ubiquitin-ligase activity. Our data establish a parkin-dependent ER-stress-associated modulation of DJ-1 and identifies p53 and XBP-1 as two major actors acting downstream of parkin in this signaling cascade in cells and in vivo. This work provides a mechanistic explanation for the increase in the unfolded protein response observed in PD pathology, i.e. that it is due to a defect in parkin-associated control of DJ-1.
DOI: 10.1242/jcs.127340
PubMed: 23447676
Affiliations:
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Le document en format XML
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uniqKey="Qi L" first="Ling" last="Qi">Ling Qi</name></author><author><name sortKey="Checler, Frederic" sort="Checler, Frederic" uniqKey="Checler F" first="Frédéric" last="Checler">Frédéric Checler</name></author><author><name sortKey="Alves Da Costa, Cristine" sort="Alves Da Costa, Cristine" uniqKey="Alves Da Costa C" first="Cristine" last="Alves Da Costa">Cristine Alves Da Costa</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23447676</idno><idno type="pmid">23447676</idno><idno type="doi">10.1242/jcs.127340</idno><idno type="wicri:Area/PubMed/Corpus">000736</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000736</idno><idno type="wicri:Area/PubMed/Curation">000704</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000704</idno><idno type="wicri:Area/PubMed/Checkpoint">000704</idno><idno type="wicri:explorRef" 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France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS/UNSA, Team Fondation pour la Recherche Médicale and Labex Distalz, 660 route des Lucioles, 06560, Sophia-Antipolis, Valbonne</wicri:regionArea><wicri:noRegion>Valbonne</wicri:noRegion><wicri:noRegion>Valbonne</wicri:noRegion></affiliation></author><author><name sortKey="Giaime, Emilie" sort="Giaime, Emilie" uniqKey="Giaime E" first="Emilie" last="Giaime">Emilie Giaime</name></author><author><name sortKey="Viotti, Julien" sort="Viotti, Julien" uniqKey="Viotti J" first="Julien" last="Viotti">Julien Viotti</name></author><author><name sortKey="Sevalle, Jean" sort="Sevalle, Jean" uniqKey="Sevalle J" first="Jean" last="Sévalle">Jean Sévalle</name></author><author><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></author><author><name sortKey="Ariga, Hiroyoshi" sort="Ariga, Hiroyoshi" uniqKey="Ariga H" first="Hiroyoshi" last="Ariga">Hiroyoshi Ariga</name></author><author><name sortKey="Qi, Ling" sort="Qi, Ling" uniqKey="Qi L" first="Ling" last="Qi">Ling Qi</name></author><author><name sortKey="Checler, Frederic" sort="Checler, Frederic" uniqKey="Checler F" first="Frédéric" last="Checler">Frédéric Checler</name></author><author><name sortKey="Alves Da Costa, Cristine" sort="Alves Da Costa, Cristine" uniqKey="Alves Da Costa C" first="Cristine" last="Alves Da Costa">Cristine Alves Da Costa</name></author></analytic><series><title level="j">Journal of cell science</title><idno type="eISSN">1477-9137</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>DNA-Binding Proteins (genetics)</term><term>DNA-Binding Proteins (metabolism)</term><term>Endoplasmic Reticulum Stress</term><term>Gene Expression Regulation (genetics)</term><term>HEK293 Cells</term><term>Humans</term><term>Intracellular Signaling Peptides and Proteins (genetics)</term><term>Intracellular Signaling Peptides and Proteins (metabolism)</term><term>Mice</term><term>Mice, Mutant Strains (genetics)</term><term>Oncogene Proteins (genetics)</term><term>Oncogene Proteins (metabolism)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Peroxiredoxins</term><term>Protein Deglycase DJ-1</term><term>Regulatory Factor X Transcription Factors</term><term>Signal Transduction (genetics)</term><term>Transcription Factors (genetics)</term><term>Transcription Factors (metabolism)</term><term>Transcription, Genetic</term><term>Tumor Suppressor Protein p53 (genetics)</term><term>Tumor Suppressor Protein p53 (metabolism)</term><term>Ubiquitin-Protein Ligases (genetics)</term><term>Ubiquitin-Protein Ligases (metabolism)</term><term>X-Box Binding Protein 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA-Binding Proteins</term><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Transcription Factors</term><term>Tumor Suppressor Protein p53</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA-Binding Proteins</term><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Transcription Factors</term><term>Tumor Suppressor Protein p53</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Gene Expression Regulation</term><term>Mice, Mutant Strains</term><term>Parkinson Disease</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Endoplasmic Reticulum Stress</term><term>HEK293 Cells</term><term>Humans</term><term>Mice</term><term>Peroxiredoxins</term><term>Protein Deglycase DJ-1</term><term>Regulatory Factor X Transcription Factors</term><term>Transcription, Genetic</term><term>X-Box Binding Protein 1</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinson's disease (PD) that have been shown to functionally interact by as-yet-unknown mechanisms. We have delineated the mechanisms by which parkin controls DJ-1. Parkin modulates DJ-1 transcription and protein levels via a signaling cascade involving p53 and the endoplasmic reticulum (ER)-stress-induced active X-box-binding protein-1S (XBP-1S). Parkin triggers the transcriptional repression of p53 while p53 downregulates DJ-1 protein and mRNA expressions. We show that parkin-mediated control of DJ-1 is fully p53-dependent. Furthermore, we establish that p53 lowers the protein and mRNA levels of XBP-1S. Accordingly, we show that parkin ultimately upregulates XBP-1 levels. Subsequently, XBP-1S physically interacts with the DJ-1 promoter, thereby enhancing its promoter trans-activation, mRNA levels and protein expression. This data was corroborated by the examination of DJ-1 in both parkin- and p53-null mice brains. This transcriptional cascade is abolished by pathogenic parkin mutations and is independent of its ubiquitin-ligase activity. Our data establish a parkin-dependent ER-stress-associated modulation of DJ-1 and identifies p53 and XBP-1 as two major actors acting downstream of parkin in this signaling cascade in cells and in vivo. This work provides a mechanistic explanation for the increase in the unfolded protein response observed in PD pathology, i.e. that it is due to a defect in parkin-associated control of DJ-1.</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Alves Da Costa, Cristine" sort="Alves Da Costa, Cristine" uniqKey="Alves Da Costa C" first="Cristine" last="Alves Da Costa">Cristine Alves Da Costa</name><name sortKey="Ariga, Hiroyoshi" sort="Ariga, Hiroyoshi" uniqKey="Ariga H" first="Hiroyoshi" last="Ariga">Hiroyoshi Ariga</name><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name><name sortKey="Checler, Frederic" sort="Checler, Frederic" uniqKey="Checler F" first="Frédéric" last="Checler">Frédéric Checler</name><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name><name sortKey="Giaime, Emilie" sort="Giaime, Emilie" uniqKey="Giaime E" first="Emilie" last="Giaime">Emilie Giaime</name><name sortKey="Qi, Ling" sort="Qi, Ling" uniqKey="Qi L" first="Ling" last="Qi">Ling Qi</name><name sortKey="Sevalle, Jean" sort="Sevalle, Jean" uniqKey="Sevalle J" first="Jean" last="Sévalle">Jean Sévalle</name><name sortKey="Viotti, Julien" sort="Viotti, Julien" uniqKey="Viotti J" first="Julien" last="Viotti">Julien Viotti</name></noCountry><country name="France"><noRegion><name sortKey="Duplan, Eric" sort="Duplan, Eric" uniqKey="Duplan E" first="Eric" last="Duplan">Eric Duplan</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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