Upregulation of human PINK1 gene expression by NFκB signalling
Identifieur interne : 000872 ( Main/Exploration ); précédent : 000871; suivant : 000873Upregulation of human PINK1 gene expression by NFκB signalling
Auteurs : Xiaoling Duan [République populaire de Chine, Canada] ; Jade Tong [Canada] ; Qin Xu [Canada] ; Yili Wu [République populaire de Chine, Canada] ; Fang Cai [Canada] ; Tingyu Li [République populaire de Chine] ; Weihong Song [République populaire de Chine, Canada]Source :
- Molecular Brain [ 1756-6606 ] ; 2014.
Abstract
Parkinson’s disease (PD) is one of the major neurodegenerative disorders. Mitochondrial malfunction is implicated in PD pathogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1), a serine/threonine kinase, plays an important role in the quality control of mitochondria and more than 70 PINK1 mutations have been identified to cause early-onset PD. However, the regulation of PINK1 gene expression remains elusive. In the present study, we identified the transcription start site (TSS) of the human PINK1 gene using switching mechanism at 5’end of RNA transcription (SMART RACE) assay. The TSS is located at 91 bp upstream of the translation start site ATG. The region with 104 bp was identified as the minimal promoter region by deletion analysis followed by dual luciferase assay. Four functional cis-acting nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-binding sites within the PINK1 promoter were identified. NFκB overexpression led to the up-regulation of PINK1 expression in both HEK293 cells and SH-SY5Y cells. Consistently, lipopolysaccharide (LPS), a strong activator of NFκB, significantly increased PINK1 expression in SH-SY5Y cells. Taken together, our results clearly suggested that PINK1 expression is tightly regulated at its transcription level and NFκB is a positive regulator for PINK1 expression.
Url:
DOI: 10.1186/s13041-014-0057-y
PubMed: 25108683
PubMed Central: 4237968
Affiliations:
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Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of 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Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation></author><author><name sortKey="Song, Weihong" sort="Song, Weihong" uniqKey="Song W" first="Weihong" last="Song">Weihong Song</name><affiliation wicri:level="1"><nlm:aff id="I1">Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, 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Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Tong, Jade" sort="Tong, Jade" uniqKey="Tong J" first="Jade" last="Tong">Jade Tong</name><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Qin" sort="Xu, Qin" uniqKey="Xu Q" first="Qin" last="Xu">Qin Xu</name><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Yili" sort="Wu, Yili" uniqKey="Wu Y" first="Yili" last="Wu">Yili Wu</name><affiliation wicri:level="1"><nlm:aff id="I1">Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Fang" sort="Cai, Fang" uniqKey="Cai F" first="Fang" last="Cai">Fang Cai</name><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Li, Tingyu" sort="Li, Tingyu" uniqKey="Li T" first="Tingyu" last="Li">Tingyu Li</name><affiliation wicri:level="1"><nlm:aff id="I1">Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation></author><author><name sortKey="Song, Weihong" sort="Song, Weihong" uniqKey="Song W" first="Weihong" last="Song">Weihong Song</name><affiliation wicri:level="1"><nlm:aff id="I1">Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014</wicri:regionArea><wicri:noRegion>Chongqing 400014</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver V6T 1Z3, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecular Brain</title><idno type="eISSN">1756-6606</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Parkinson’s disease (PD) is one of the major neurodegenerative disorders. Mitochondrial malfunction is implicated in PD pathogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1), a serine/threonine kinase, plays an important role in the quality control of mitochondria and more than 70 PINK1 mutations have been identified to cause early-onset PD. However, the regulation of PINK1 gene expression remains elusive. In the present study, we identified the transcription start site (TSS) of the human PINK1 gene using switching mechanism at 5’end of RNA transcription (SMART RACE) assay. The TSS is located at 91 bp upstream of the translation start site ATG. The region with 104 bp was identified as the minimal promoter region by deletion analysis followed by dual luciferase assay. Four functional cis-acting nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-binding sites within the PINK1 promoter were identified. NFκB overexpression led to the up-regulation of PINK1 expression in both HEK293 cells and SH-SY5Y cells. Consistently, lipopolysaccharide (LPS), a strong activator of NFκB, significantly increased PINK1 expression in SH-SY5Y cells. Taken together, our results clearly suggested that PINK1 expression is tightly regulated at its transcription level and NFκB is a positive regulator for PINK1 expression.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Van Den Eeden, Sk" uniqKey="Van Den Eeden S">SK Van Den Eeden</name></author><author><name sortKey="Tanner, Cm" uniqKey="Tanner C">CM Tanner</name></author><author><name sortKey="Bernstein, Al" uniqKey="Bernstein A">AL Bernstein</name></author><author><name sortKey="Fross, Rd" uniqKey="Fross R">RD Fross</name></author><author><name sortKey="Leimpeter, A" uniqKey="Leimpeter A">A Leimpeter</name></author><author><name sortKey="Bloch, Da" uniqKey="Bloch D">DA Bloch</name></author><author><name sortKey="Nelson, Lm" uniqKey="Nelson L">LM Nelson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Parkinson, J" uniqKey="Parkinson J">J 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Arboleda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muqit, Mm" uniqKey="Muqit M">MM Muqit</name></author><author><name sortKey="Abou Sleiman, Pm" uniqKey="Abou Sleiman P">PM Abou-Sleiman</name></author><author><name sortKey="Saurin, At" uniqKey="Saurin A">AT Saurin</name></author><author><name sortKey="Harvey, K" uniqKey="Harvey K">K Harvey</name></author><author><name sortKey="Gandhi, S" uniqKey="Gandhi S">S Gandhi</name></author><author><name sortKey="Deas, E" uniqKey="Deas E">E Deas</name></author><author><name sortKey="Eaton, S" uniqKey="Eaton S">S Eaton</name></author><author><name sortKey="Payne Smith, Md" uniqKey="Payne Smith M">MD Payne Smith</name></author><author><name sortKey="Venner, K" uniqKey="Venner K">K Venner</name></author><author><name sortKey="Matilla, A" uniqKey="Matilla A">A Matilla</name></author><author><name sortKey="Healy, Dg" uniqKey="Healy D">DG Healy</name></author><author><name sortKey="Gilks, Wp" uniqKey="Gilks 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uniqKey="Kawarabayashi T">T Kawarabayashi</name></author><author><name sortKey="Nagai, M" uniqKey="Nagai M">M Nagai</name></author><author><name sortKey="Ohta, Y" uniqKey="Ohta Y">Y Ohta</name></author><author><name sortKey="Deguchi, K" uniqKey="Deguchi K">K Deguchi</name></author><author><name sortKey="Kurata, T" uniqKey="Kurata T">T Kurata</name></author><author><name sortKey="Morimoto, N" uniqKey="Morimoto N">N Morimoto</name></author><author><name sortKey="Takehisa, Y" uniqKey="Takehisa Y">Y Takehisa</name></author><author><name sortKey="Matsubara, E" uniqKey="Matsubara E">E Matsubara</name></author><author><name sortKey="Ikeda, M" uniqKey="Ikeda M">M Ikeda</name></author><author><name sortKey="Harigaya, Y" uniqKey="Harigaya Y">Y Harigaya</name></author><author><name sortKey="Shoji, M" uniqKey="Shoji M">M Shoji</name></author><author><name sortKey="Takahashi, R" uniqKey="Takahashi R">R Takahashi</name></author><author><name sortKey="Abe, K" uniqKey="Abe K">K Abe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qing, H" uniqKey="Qing H">H Qing</name></author><author><name sortKey="Zhou, W" uniqKey="Zhou W">W Zhou</name></author><author><name sortKey="Christensen, Ma" uniqKey="Christensen M">MA Christensen</name></author><author><name sortKey="Sun, X" uniqKey="Sun X">X Sun</name></author><author><name sortKey="Tong, Y" uniqKey="Tong Y">Y Tong</name></author><author><name sortKey="Song, W" uniqKey="Song W">W Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Nadeau, P" uniqKey="Nadeau P">P Nadeau</name></author><author><name sortKey="Song, W" uniqKey="Song W">W Song</name></author><author><name sortKey="Donoviel, D" uniqKey="Donoviel D">D Donoviel</name></author><author><name sortKey="Yuan, M" uniqKey="Yuan M">M Yuan</name></author><author><name sortKey="Bernstein, A" uniqKey="Bernstein A">A Bernstein</name></author><author><name sortKey="Yankner, Ba" uniqKey="Yankner B">BA Yankner</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Duan, Xiaoling" sort="Duan, Xiaoling" uniqKey="Duan X" first="Xiaoling" last="Duan">Xiaoling Duan</name></noRegion><name sortKey="Li, Tingyu" sort="Li, Tingyu" uniqKey="Li T" first="Tingyu" last="Li">Tingyu Li</name><name sortKey="Song, Weihong" sort="Song, Weihong" uniqKey="Song W" first="Weihong" last="Song">Weihong Song</name><name sortKey="Wu, Yili" sort="Wu, Yili" uniqKey="Wu Y" first="Yili" last="Wu">Yili Wu</name></country><country name="Canada"><noRegion><name sortKey="Duan, Xiaoling" sort="Duan, Xiaoling" uniqKey="Duan X" first="Xiaoling" last="Duan">Xiaoling Duan</name></noRegion><name sortKey="Cai, Fang" sort="Cai, Fang" uniqKey="Cai F" first="Fang" last="Cai">Fang Cai</name><name sortKey="Song, Weihong" sort="Song, Weihong" uniqKey="Song W" first="Weihong" last="Song">Weihong Song</name><name sortKey="Tong, Jade" sort="Tong, Jade" uniqKey="Tong J" first="Jade" last="Tong">Jade Tong</name><name sortKey="Wu, Yili" sort="Wu, Yili" uniqKey="Wu Y" first="Yili" last="Wu">Yili Wu</name><name sortKey="Xu, Qin" sort="Xu, Qin" uniqKey="Xu Q" first="Qin" last="Xu">Qin Xu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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