The pathogenic human Torsin A in Drosophila activates the unfolded protein response and increases susceptibility to oxidative stress
Identifieur interne : 000230 ( Pmc/Curation ); précédent : 000229; suivant : 000231The pathogenic human Torsin A in Drosophila activates the unfolded protein response and increases susceptibility to oxidative stress
Auteurs : A-Young Kim ; Jong Bok Seo ; Won-Tae Kim [Corée du Sud] ; Hee Jeong Choi ; Soo-Young Kim ; Genevieve Morrow ; Robert M. Tanguay ; Hermann Steller [États-Unis] ; Young Ho KohSource :
- BMC Genomics [ 1471-2164 ] ; 2015.
Abstract
Dystonia1 (DYT1) dystonia is caused by a glutamic acid deletion (ΔE) mutation in the gene encoding Torsin A in humans (HTorA). To investigate the unknown molecular and cellular mechanisms underlying DYT1 dystonia, we performed an unbiased proteomic analysis.
We found that the amount of proteins and transcripts of an Endoplasmic reticulum (ER) resident chaperone Heat shock protein cognate 3 (HSC3) and a mitochondria chaperone Heat Shock Protein 22 (HSP22) were significantly increased in the HTorAΔE– expressing brains compared to the normal HTorA (HTorAWT) expressing brains. The physiological consequences included an increased susceptibility to oxidative and ER stress compared to normal HTorAWT flies. The alteration of transcripts of Inositol-requiring enzyme-1 (IRE1)-dependent spliced X box binding protein 1(Xbp1), several ER chaperones, a nucleotide exchange factor, Autophagy related protein 8b (ATG8b) and components of the ER associated degradation (ERAD) pathway and increased expression of the Xbp1-enhanced Green Fluorescence Protein (eGFP) in HTorAΔE brains strongly indicated the activation of the unfolded protein response (UPR). In addition, perturbed expression of the UPR sensors and inducers in the HTorAΔE
Taken together, these data show that HTorAΔE in
The online version of this article (doi:10.1186/s12864-015-1518-0) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12864-015-1518-0
PubMed: 25903460
PubMed Central: 4415242
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000230
Links to Exploration step
PMC:4415242Curation
No country items
A-Young Kim<affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3">Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Seoul 136-713 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3">Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Seoul 136-713 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff5">Department of Molecular Biology, Medical Biochemistry & Pathology, Université Laval, Québec, Qc G1V 0A6 Canada</nlm:aff><wicri:noCountry code="subfield">Qc G1V 0A6 Canada</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff5">Department of Molecular Biology, Medical Biochemistry & Pathology, Université Laval, Québec, Qc G1V 0A6 Canada</nlm:aff><wicri:noCountry code="subfield">Qc G1V 0A6 Canada</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The pathogenic human Torsin A in <italic>Drosophila</italic> activates the unfolded protein response and increases susceptibility to oxidative stress</title><author><name sortKey="Kim, A Young" sort="Kim, A Young" uniqKey="Kim A" first="A-Young" last="Kim">A-Young Kim</name><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Seo, Jong Bok" sort="Seo, Jong Bok" uniqKey="Seo J" first="Jong Bok" last="Seo">Jong Bok Seo</name><affiliation><nlm:aff id="Aff3">Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Seoul 136-713 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Kim, Won Tae" sort="Kim, Won Tae" uniqKey="Kim W" first="Won-Tae" last="Kim">Won-Tae Kim</name><affiliation wicri:level="1"><nlm:aff id="Aff4">National Academy of Agricultural Science, Rural Development Administration, Suwon, 441-707 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>National Academy of Agricultural Science, Rural Development Administration, Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Choi, Hee Jeong" sort="Choi, Hee Jeong" uniqKey="Choi H" first="Hee Jeong" last="Choi">Hee Jeong Choi</name><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Kim, Soo Young" sort="Kim, Soo Young" uniqKey="Kim S" first="Soo-Young" last="Kim">Soo-Young Kim</name><affiliation><nlm:aff id="Aff3">Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Seoul 136-713 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Morrow, Genevieve" sort="Morrow, Genevieve" uniqKey="Morrow G" first="Genevieve" last="Morrow">Genevieve Morrow</name><affiliation><nlm:aff id="Aff5">Department of Molecular Biology, Medical Biochemistry & Pathology, Université Laval, Québec, Qc G1V 0A6 Canada</nlm:aff><wicri:noCountry code="subfield">Qc G1V 0A6 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Tanguay, Robert M" sort="Tanguay, Robert M" uniqKey="Tanguay R" first="Robert M" last="Tanguay">Robert M. Tanguay</name><affiliation><nlm:aff id="Aff5">Department of Molecular Biology, Medical Biochemistry & Pathology, Université Laval, Québec, Qc G1V 0A6 Canada</nlm:aff><wicri:noCountry code="subfield">Qc G1V 0A6 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Steller, Hermann" sort="Steller, Hermann" uniqKey="Steller H" first="Hermann" last="Steller">Hermann Steller</name><affiliation wicri:level="2"><nlm:aff id="Aff6">Howard Hughes Medical Institute, the Rockefeller University, New York, NY 10065 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Howard Hughes Medical Institute, the Rockefeller University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Koh, Young Ho" sort="Koh, Young Ho" uniqKey="Koh Y" first="Young Ho" last="Koh">Young Ho Koh</name><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25903460</idno><idno type="pmc">4415242</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415242</idno><idno type="RBID">PMC:4415242</idno><idno type="doi">10.1186/s12864-015-1518-0</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000230</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000230</idno><idno type="wicri:Area/Pmc/Curation">000230</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000230</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The pathogenic human Torsin A in <italic>Drosophila</italic> activates the unfolded protein response and increases susceptibility to oxidative stress</title><author><name sortKey="Kim, A Young" sort="Kim, A Young" uniqKey="Kim A" first="A-Young" last="Kim">A-Young Kim</name><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Seo, Jong Bok" sort="Seo, Jong Bok" uniqKey="Seo J" first="Jong Bok" last="Seo">Jong Bok Seo</name><affiliation><nlm:aff id="Aff3">Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Seoul 136-713 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Kim, Won Tae" sort="Kim, Won Tae" uniqKey="Kim W" first="Won-Tae" last="Kim">Won-Tae Kim</name><affiliation wicri:level="1"><nlm:aff id="Aff4">National Academy of Agricultural Science, Rural Development Administration, Suwon, 441-707 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>National Academy of Agricultural Science, Rural Development Administration, Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Choi, Hee Jeong" sort="Choi, Hee Jeong" uniqKey="Choi H" first="Hee Jeong" last="Choi">Hee Jeong Choi</name><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Kim, Soo Young" sort="Kim, Soo Young" uniqKey="Kim S" first="Soo-Young" last="Kim">Soo-Young Kim</name><affiliation><nlm:aff id="Aff3">Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Seoul 136-713 Republic of Korea</wicri:noCountry></affiliation></author><author><name sortKey="Morrow, Genevieve" sort="Morrow, Genevieve" uniqKey="Morrow G" first="Genevieve" last="Morrow">Genevieve Morrow</name><affiliation><nlm:aff id="Aff5">Department of Molecular Biology, Medical Biochemistry & Pathology, Université Laval, Québec, Qc G1V 0A6 Canada</nlm:aff><wicri:noCountry code="subfield">Qc G1V 0A6 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Tanguay, Robert M" sort="Tanguay, Robert M" uniqKey="Tanguay R" first="Robert M" last="Tanguay">Robert M. Tanguay</name><affiliation><nlm:aff id="Aff5">Department of Molecular Biology, Medical Biochemistry & Pathology, Université Laval, Québec, Qc G1V 0A6 Canada</nlm:aff><wicri:noCountry code="subfield">Qc G1V 0A6 Canada</wicri:noCountry></affiliation></author><author><name sortKey="Steller, Hermann" sort="Steller, Hermann" uniqKey="Steller H" first="Hermann" last="Steller">Hermann Steller</name><affiliation wicri:level="2"><nlm:aff id="Aff6">Howard Hughes Medical Institute, the Rockefeller University, New York, NY 10065 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Howard Hughes Medical Institute, the Rockefeller University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Koh, Young Ho" sort="Koh, Young Ho" uniqKey="Koh Y" first="Young Ho" last="Koh">Young Ho Koh</name><affiliation><nlm:aff id="Aff1">ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gyeonggido 431-060 Republic of Korea</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2">Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</nlm:aff><wicri:noCountry code="subfield">Gangwon-do 200-702 Republic of Korea</wicri:noCountry></affiliation></author></analytic><series><title level="j">BMC Genomics</title><idno type="eISSN">1471-2164</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Dystonia1 (DYT1) dystonia is caused by a glutamic acid deletion (ΔE) mutation in the gene encoding Torsin A in humans (HTorA). To investigate the unknown molecular and cellular mechanisms underlying DYT1 dystonia, we performed an unbiased proteomic analysis.</p></sec><sec><title>Results</title><p>We found that the amount of proteins and transcripts of an Endoplasmic reticulum (ER) resident chaperone Heat shock protein cognate 3 (HSC3) and a mitochondria chaperone Heat Shock Protein 22 (HSP22) were significantly increased in the HTorA<sup>ΔE</sup>– expressing brains compared to the normal HTorA (HTorA<sup>WT</sup>) expressing brains. The physiological consequences included an increased susceptibility to oxidative and ER stress compared to normal HTorA<sup>WT</sup> flies. The alteration of transcripts of Inositol-requiring enzyme-1 (IRE1)-dependent spliced X box binding protein 1(Xbp1), several ER chaperones, a nucleotide exchange factor, Autophagy related protein 8b (ATG8b) and components of the ER associated degradation (ERAD) pathway and increased expression of the Xbp1-enhanced Green Fluorescence Protein (eGFP) in HTorA<sup>ΔE</sup> brains strongly indicated the activation of the unfolded protein response (UPR). In addition, perturbed expression of the UPR sensors and inducers in the HTorA<sup>ΔE</sup><italic>Drosophila</italic> brains resulted in a significantly reduced life span of the flies. Furthermore, the types and quantities of proteins present in the anti-HSC3 positive microsomes in the HTorA<sup>ΔE</sup> brains were different from those of the HTorA<sup>WT</sup> brains.</p></sec><sec><title>Conclusion</title><p>Taken together, these data show that HTorA<sup>ΔE</sup> in <italic>Drosophila</italic> brains may activate the UPR and increase the expression of HSP22 to compensate for the toxic effects caused by HTorA<sup>ΔE</sup> in the brains.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s12864-015-1518-0) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mcnaught, Ksp" uniqKey="Mcnaught K">KSP McNaught</name></author><author><name sortKey="Kapustin, A" uniqKey="Kapustin A">A Kapustin</name></author><author><name sortKey="Jackson, T" uniqKey="Jackson T">T Jackson</name></author><author><name sortKey="Jengelley, T A" uniqKey="Jengelley T">T-A Jengelley</name></author><author><name sortKey="Jnobaptiste, R" uniqKey="Jnobaptiste R">R JnoBaptiste</name></author><author><name sortKey="Shashidharan, P" uniqKey="Shashidharan P">P Shashidharan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ross, Ca" uniqKey="Ross C">CA Ross</name></author><author><name sortKey="Poirier, Ma" uniqKey="Poirier M">MA Poirier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peter, Ob" uniqKey="Peter O">OB Peter</name></author><author><name sortKey="Nobuyuki, N" uniqKey="Nobuyuki N">N Nobuyuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, Jh" uniqKey="Lin J">JH Lin</name></author><author><name sortKey="Walter, P" uniqKey="Walter P">P Walter</name></author><author><name sortKey="Yen, Tsb" uniqKey="Yen T">TSB Yen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scheper, W" uniqKey="Scheper W">W Scheper</name></author><author><name sortKey="Hoozemans, Jjm" uniqKey="Hoozemans J">JJM Hoozemans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, I" uniqKey="Kim I">I Kim</name></author><author><name sortKey="Xu, W" uniqKey="Xu W">W Xu</name></author><author><name sortKey="Reed, Jc" uniqKey="Reed J">JC Reed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dudek, J" uniqKey="Dudek J">J Dudek</name></author><author><name sortKey="Benedix, J" uniqKey="Benedix J">J Benedix</name></author><author><name sortKey="Cappel, S" uniqKey="Cappel S">S Cappel</name></author><author><name sortKey="Greiner, M" uniqKey="Greiner M">M Greiner</name></author><author><name sortKey="Jalal, C" uniqKey="Jalal C">C Jalal</name></author><author><name sortKey="Muller, L" uniqKey="Muller L">L Müller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rasheva, V" uniqKey="Rasheva V">V Rasheva</name></author><author><name sortKey="Domingos, P" uniqKey="Domingos P">P Domingos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mendes, Cs" uniqKey="Mendes C">CS Mendes</name></author><author><name sortKey="Levet, C" uniqKey="Levet C">C Levet</name></author><author><name sortKey="Chatelain, G" uniqKey="Chatelain G">G Chatelain</name></author><author><name sortKey="Dourlen, P" uniqKey="Dourlen P">P Dourlen</name></author><author><name sortKey="Fouillet, A" uniqKey="Fouillet A">A Fouillet</name></author><author><name sortKey="Dichtel Danjoy, M L" uniqKey="Dichtel Danjoy M">M-L Dichtel-Danjoy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoozemans, Jjm" uniqKey="Hoozemans J">JJM Hoozemans</name></author><author><name sortKey="Van Haastert, Es" uniqKey="Van Haastert E">ES van Haastert</name></author><author><name sortKey="Nijholt, Dat" uniqKey="Nijholt D">DAT Nijholt</name></author><author><name sortKey="Rozemuller, Ajm" uniqKey="Rozemuller A">AJM Rozemuller</name></author><author><name sortKey="Eikelenboom, P" uniqKey="Eikelenboom P">P Eikelenboom</name></author><author><name sortKey="Scheper, W" uniqKey="Scheper W">W Scheper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, Ct" uniqKey="Chu C">CT Chu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hetz, C" uniqKey="Hetz C">C Hetz</name></author><author><name sortKey="Thielen, P" uniqKey="Thielen P">P Thielen</name></author><author><name sortKey="Matus, S" uniqKey="Matus S">S Matus</name></author><author><name sortKey="Nassif, M" uniqKey="Nassif M">M Nassif</name></author><author><name sortKey="Court, F" uniqKey="Court F">F Court</name></author><author><name sortKey="Kiffin, R" uniqKey="Kiffin R">R Kiffin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ozelius, Lj" uniqKey="Ozelius L">LJ Ozelius</name></author><author><name sortKey="Hewett, Jw" uniqKey="Hewett J">JW Hewett</name></author><author><name sortKey="Page, Ce" uniqKey="Page C">CE Page</name></author><author><name sortKey="Bressman, Sb" uniqKey="Bressman S">SB Bressman</name></author><author><name sortKey="Kramer, Pl" uniqKey="Kramer P">PL Kramer</name></author><author><name sortKey="Shalish, C" uniqKey="Shalish C">C Shalish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Risch, Nj" uniqKey="Risch N">NJ Risch</name></author><author><name sortKey="Bressman, Sb" uniqKey="Bressman S">SB Bressman</name></author><author><name sortKey="Senthil, G" uniqKey="Senthil G">G Senthil</name></author><author><name sortKey="Ozelius, Lj" uniqKey="Ozelius L">LJ Ozelius</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Granata, A" uniqKey="Granata A">A Granata</name></author><author><name sortKey="Schiavo, G" uniqKey="Schiavo G">G Schiavo</name></author><author><name sortKey="Warner, Tt" uniqKey="Warner T">TT Warner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neuwald, Af" uniqKey="Neuwald A">AF Neuwald</name></author><author><name sortKey="Aravind, L" uniqKey="Aravind L">L Aravind</name></author><author><name sortKey="Spouge, Jl" uniqKey="Spouge J">JL Spouge</name></author><author><name sortKey="Koonin, Ev" uniqKey="Koonin E">EV Koonin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hewett, Jw" uniqKey="Hewett J">JW Hewett</name></author><author><name sortKey="Tannous, B" uniqKey="Tannous B">B Tannous</name></author><author><name sortKey="Niland, Bp" uniqKey="Niland B">BP Niland</name></author><author><name sortKey="Nery, Fc" uniqKey="Nery F">FC Nery</name></author><author><name sortKey="Zeng, J" uniqKey="Zeng J">J Zeng</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hewett, Jw" uniqKey="Hewett J">JW Hewett</name></author><author><name sortKey="Nery, Fc" uniqKey="Nery F">FC Nery</name></author><author><name sortKey="Niland, B" uniqKey="Niland B">B Niland</name></author><author><name sortKey="Ge, P" uniqKey="Ge P">P Ge</name></author><author><name sortKey="Tan, P" uniqKey="Tan P">P Tan</name></author><author><name sortKey="Hadwiger, P" uniqKey="Hadwiger P">P Hadwiger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goodchild, Re" uniqKey="Goodchild R">RE Goodchild</name></author><author><name sortKey="Dauer, Wt" uniqKey="Dauer W">WT Dauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dang, Mt" uniqKey="Dang M">MT Dang</name></author><author><name sortKey="Yokoi, F" uniqKey="Yokoi F">F Yokoi</name></author><author><name sortKey="Mcnaught, Ksp" uniqKey="Mcnaught K">KSP McNaught</name></author><author><name sortKey="Jengelley, T A" uniqKey="Jengelley T">T-A Jengelley</name></author><author><name sortKey="Jackson, T" uniqKey="Jackson T">T Jackson</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shashidharan, P" uniqKey="Shashidharan P">P Shashidharan</name></author><author><name sortKey="Sandu, D" uniqKey="Sandu D">D Sandu</name></author><author><name sortKey="Potla, U" uniqKey="Potla U">U Potla</name></author><author><name sortKey="Armata, Ia" uniqKey="Armata I">IA Armata</name></author><author><name sortKey="Walker, Rh" uniqKey="Walker R">RH Walker</name></author><author><name sortKey="Mcnaught, Ks" uniqKey="Mcnaught K">KS McNaught</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goodchild, Re" uniqKey="Goodchild R">RE Goodchild</name></author><author><name sortKey="Dauer, Wt" uniqKey="Dauer W">WT Dauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naismith, Tv" uniqKey="Naismith T">TV Naismith</name></author><author><name sortKey="Dalal, S" uniqKey="Dalal S">S Dalal</name></author><author><name sortKey="Hanson, Pi" uniqKey="Hanson P">PI Hanson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hewett, Jw" uniqKey="Hewett J">JW Hewett</name></author><author><name sortKey="Zeng, J" uniqKey="Zeng J">J Zeng</name></author><author><name sortKey="Niland, Bp" uniqKey="Niland B">BP Niland</name></author><author><name sortKey="Bragg, Dc" uniqKey="Bragg D">DC Bragg</name></author><author><name sortKey="Breakefield, Xo" uniqKey="Breakefield X">XO Breakefield</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kamm, C" uniqKey="Kamm C">C Kamm</name></author><author><name sortKey="Boston, H" uniqKey="Boston H">H Boston</name></author><author><name sortKey="Hewett, J" uniqKey="Hewett J">J Hewett</name></author><author><name sortKey="Wilbur, J" uniqKey="Wilbur J">J Wilbur</name></author><author><name sortKey="Corey, Dp" uniqKey="Corey D">DP Corey</name></author><author><name sortKey="Hanson, Pi" uniqKey="Hanson P">PI Hanson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Ce" uniqKey="Kim C">CE Kim</name></author><author><name sortKey="Perez, A" uniqKey="Perez A">A Perez</name></author><author><name sortKey="Perkins, G" uniqKey="Perkins G">G Perkins</name></author><author><name sortKey="Ellisman, Mh" uniqKey="Ellisman M">MH Ellisman</name></author><author><name sortKey="Dauer, Wt" uniqKey="Dauer W">WT Dauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin, Jn" uniqKey="Martin J">JN Martin</name></author><author><name sortKey="Bair, Tb" uniqKey="Bair T">TB Bair</name></author><author><name sortKey="Bode, N" uniqKey="Bode N">N Bode</name></author><author><name sortKey="Dauer, Wt" uniqKey="Dauer W">WT Dauer</name></author><author><name sortKey="Gonzalez Alegre, P" uniqKey="Gonzalez Alegre P">P Gonzalez-Alegre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walter, M" uniqKey="Walter M">M Walter</name></author><author><name sortKey="Bonin, M" uniqKey="Bonin M">M Bonin</name></author><author><name sortKey="Pullman, Rs" uniqKey="Pullman R">RS Pullman</name></author><author><name sortKey="Valente, Em" uniqKey="Valente E">EM Valente</name></author><author><name sortKey="Loi, M" uniqKey="Loi M">M Loi</name></author><author><name sortKey="Gambarin, M" uniqKey="Gambarin M">M Gambarin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koh, Y H" uniqKey="Koh Y">Y-H Koh</name></author><author><name sortKey="Rehfeld, K" uniqKey="Rehfeld K">K Rehfeld</name></author><author><name sortKey="Ganetzky, B" uniqKey="Ganetzky B">B Ganetzky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Dw" uniqKey="Lee D">DW Lee</name></author><author><name sortKey="Seo, Jb" uniqKey="Seo J">JB Seo</name></author><author><name sortKey="Ganetzky, B" uniqKey="Ganetzky B">B Ganetzky</name></author><author><name sortKey="Koh, Yh" uniqKey="Koh Y">YH Koh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ryoo, Hd" uniqKey="Ryoo H">HD Ryoo</name></author><author><name sortKey="Domingos, Pm" uniqKey="Domingos P">PM Domingos</name></author><author><name sortKey="Kang, M J" uniqKey="Kang M">M-J Kang</name></author><author><name sortKey="Steller, H" uniqKey="Steller H">H Steller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, D W" uniqKey="Lee D">D-W Lee</name></author><author><name sortKey="Seo, Jb" uniqKey="Seo J">JB Seo</name></author><author><name sortKey="Nam, Mh" uniqKey="Nam M">MH Nam</name></author><author><name sortKey="Kang, Js" uniqKey="Kang J">JS Kang</name></author><author><name sortKey="Kim, Sy" uniqKey="Kim S">SY Kim</name></author><author><name sortKey="Kim, Ay" uniqKey="Kim A">AY Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Y" uniqKey="Park Y">Y Park</name></author><author><name sortKey="Kim, W" uniqKey="Kim W">W Kim</name></author><author><name sortKey="Kim, Ay" uniqKey="Kim A">AY Kim</name></author><author><name sortKey="Choi, Hj" uniqKey="Choi H">HJ Choi</name></author><author><name sortKey="Choi, Jk" uniqKey="Choi J">JK Choi</name></author><author><name sortKey="Park, N" uniqKey="Park N">N Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morrow, G" uniqKey="Morrow G">G Morrow</name></author><author><name sortKey="Inaguma, Y" uniqKey="Inaguma Y">Y Inaguma</name></author><author><name sortKey="Kato, K" uniqKey="Kato K">K Kato</name></author><author><name sortKey="Tanguay, Rm" uniqKey="Tanguay R">RM Tanguay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miwa, S" uniqKey="Miwa S">S Miwa</name></author><author><name sortKey="St Pierre, J" uniqKey="St Pierre J">J St-Pierre</name></author><author><name sortKey="Partridge, L" uniqKey="Partridge L">L Partridge</name></author><author><name sortKey="Brand, Md" uniqKey="Brand M">MD Brand</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morrow, G" uniqKey="Morrow G">G Morrow</name></author><author><name sortKey="Samson, M" uniqKey="Samson M">M Samson</name></author><author><name sortKey="Michaud, S" uniqKey="Michaud S">S Michaud</name></author><author><name sortKey="Tanguay, Rm" uniqKey="Tanguay R">RM Tanguay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bustin, Sa" uniqKey="Bustin S">SA Bustin</name></author><author><name sortKey="Benes, V" uniqKey="Benes V">V Benes</name></author><author><name sortKey="Garson, Ja" uniqKey="Garson J">JA Garson</name></author><author><name sortKey="Hellemans, J" uniqKey="Hellemans J">J Hellemans</name></author><author><name sortKey="Huggett, J" uniqKey="Huggett J">J Huggett</name></author><author><name sortKey="Kubista, M" uniqKey="Kubista M">M Kubista</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meulener, M" uniqKey="Meulener M">M Meulener</name></author><author><name sortKey="Whitworth, Aj" uniqKey="Whitworth A">AJ Whitworth</name></author><author><name sortKey="Armstrong Gold, Ce" uniqKey="Armstrong Gold C">CE Armstrong-Gold</name></author><author><name sortKey="Rizzu, P" uniqKey="Rizzu P">P Rizzu</name></author><author><name sortKey="Heutink, P" uniqKey="Heutink P">P Heutink</name></author><author><name sortKey="Wes, Pd" uniqKey="Wes P">PD Wes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xia, W" uniqKey="Xia W">W Xia</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Ostaszewski, Bl" uniqKey="Ostaszewski B">BL Ostaszewski</name></author><author><name sortKey="Kimberly, Wt" uniqKey="Kimberly W">WT Kimberly</name></author><author><name sortKey="Seubert, P" uniqKey="Seubert P">P Seubert</name></author><author><name sortKey="Koo, Eh" uniqKey="Koo E">EH Koo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Djl" uniqKey="Tan D">DJL Tan</name></author><author><name sortKey="Dvinge, H" uniqKey="Dvinge H">H Dvinge</name></author><author><name sortKey="Christoforou, A" uniqKey="Christoforou A">A Christoforou</name></author><author><name sortKey="Bertone, P" uniqKey="Bertone P">P Bertone</name></author><author><name sortKey="Martinez Arias, A" uniqKey="Martinez Arias A">A Martinez Arias</name></author><author><name sortKey="Lilley, Ks" uniqKey="Lilley K">KS Lilley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ono, M" uniqKey="Ono M">M Ono</name></author><author><name sortKey="Shitashige, M" uniqKey="Shitashige M">M Shitashige</name></author><author><name sortKey="Honda, K" uniqKey="Honda K">K Honda</name></author><author><name sortKey="Isobe, T" uniqKey="Isobe T">T Isobe</name></author><author><name sortKey="Kuwabara, H" uniqKey="Kuwabara H">H Kuwabara</name></author><author><name sortKey="Matsuzuki, H" uniqKey="Matsuzuki H">H Matsuzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, B B" uniqKey="Gao B">B-B Gao</name></author><author><name sortKey="Stuart, L" uniqKey="Stuart L">L Stuart</name></author><author><name sortKey="Feener, Ep" uniqKey="Feener E">EP Feener</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loewen, Ca" uniqKey="Loewen C">CA Loewen</name></author><author><name sortKey="Feany, Mb" uniqKey="Feany M">MB Feany</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hewett, J" uniqKey="Hewett J">J Hewett</name></author><author><name sortKey="Gonzalez Agosti, C" uniqKey="Gonzalez Agosti C">C Gonzalez-Agosti</name></author><author><name sortKey="Slater, D" uniqKey="Slater D">D Slater</name></author><author><name sortKey="Ziefer, P" uniqKey="Ziefer P">P Ziefer</name></author><author><name sortKey="Li, S" uniqKey="Li S">S Li</name></author><author><name sortKey="Bergeron, D" uniqKey="Bergeron D">D Bergeron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kustedjo, K" uniqKey="Kustedjo K">K Kustedjo</name></author><author><name sortKey="Bracey, Mh" uniqKey="Bracey M">MH Bracey</name></author><author><name sortKey="Cravatt, Bf" uniqKey="Cravatt B">BF Cravatt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Landis, Gn" uniqKey="Landis G">GN Landis</name></author><author><name sortKey="Abdueva, D" uniqKey="Abdueva D">D Abdueva</name></author><author><name sortKey="Skvortsov, D" uniqKey="Skvortsov D">D Skvortsov</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Rabin, Be" uniqKey="Rabin B">BE Rabin</name></author><author><name sortKey="Carrick, J" uniqKey="Carrick J">J Carrick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carbone, Ma" uniqKey="Carbone M">MA Carbone</name></author><author><name sortKey="Ayroles, Jf" uniqKey="Ayroles J">JF Ayroles</name></author><author><name sortKey="Yamamoto, A" uniqKey="Yamamoto A">A Yamamoto</name></author><author><name sortKey="Morozova, Tv" uniqKey="Morozova T">TV Morozova</name></author><author><name sortKey="West, Sa" uniqKey="West S">SA West</name></author><author><name sortKey="Magwire, Mm" uniqKey="Magwire M">MM Magwire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fouillet, A" uniqKey="Fouillet A">A Fouillet</name></author><author><name sortKey="Levet, C" uniqKey="Levet C">C Levet</name></author><author><name sortKey="Virgone, A" uniqKey="Virgone A">A Virgone</name></author><author><name sortKey="Robin, M" uniqKey="Robin M">M Robin</name></author><author><name sortKey="Dourlen, P" uniqKey="Dourlen P">P Dourlen</name></author><author><name sortKey="Rieusset, J" uniqKey="Rieusset J">J Rieusset</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Todd, Dj" uniqKey="Todd D">DJ Todd</name></author><author><name sortKey="Lee, A H" uniqKey="Lee A">A-H Lee</name></author><author><name sortKey="Glimcher, Lh" uniqKey="Glimcher L">LH Glimcher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ron, D" uniqKey="Ron D">D Ron</name></author><author><name sortKey="Walter, P" uniqKey="Walter P">P Walter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marciniak, Sj" uniqKey="Marciniak S">SJ Marciniak</name></author><author><name sortKey="Ron, D" uniqKey="Ron D">D Ron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hebert, Dn" uniqKey="Hebert D">DN Hebert</name></author><author><name sortKey="Molinari, M" uniqKey="Molinari M">M Molinari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mi, H" uniqKey="Mi H">H Mi</name></author><author><name sortKey="Dong, Q" uniqKey="Dong Q">Q Dong</name></author><author><name sortKey="Muruganujan, A" uniqKey="Muruganujan A">A Muruganujan</name></author><author><name sortKey="Gaudet, P" uniqKey="Gaudet P">P Gaudet</name></author><author><name sortKey="Lewis, S" uniqKey="Lewis S">S Lewis</name></author><author><name sortKey="Thomas, Pd" uniqKey="Thomas P">PD Thomas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carbon, S" uniqKey="Carbon S">S Carbon</name></author><author><name sortKey="Ireland, A" uniqKey="Ireland A">A Ireland</name></author><author><name sortKey="Mungall, Cj" uniqKey="Mungall C">CJ Mungall</name></author><author><name sortKey="Shu, S" uniqKey="Shu S">S Shu</name></author><author><name sortKey="Marshall, B" uniqKey="Marshall B">B Marshall</name></author><author><name sortKey="Lewis, S" uniqKey="Lewis S">S Lewis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mendes, Hf" uniqKey="Mendes H">HF Mendes</name></author><author><name sortKey="Cheetham, Me" uniqKey="Cheetham M">ME Cheetham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holst, B" uniqKey="Holst B">B Holst</name></author><author><name sortKey="Tachibana, C" uniqKey="Tachibana C">C Tachibana</name></author><author><name sortKey="Winther, Jr" uniqKey="Winther J">JR Winther</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kang, M J" uniqKey="Kang M">M-J Kang</name></author><author><name sortKey="Ryoo, Hd" uniqKey="Ryoo H">HD Ryoo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giles, Lm" uniqKey="Giles L">LM Giles</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Li, L" uniqKey="Li L">L Li</name></author><author><name sortKey="Chin, L S" uniqKey="Chin L">L-S Chin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simonsen, A" uniqKey="Simonsen A">A Simonsen</name></author><author><name sortKey="Cumming, Rc" uniqKey="Cumming R">RC Cumming</name></author><author><name sortKey="Brech, A" uniqKey="Brech A">A Brech</name></author><author><name sortKey="Isakson, P" uniqKey="Isakson P">P Isakson</name></author><author><name sortKey="Schubert, Dr" uniqKey="Schubert D">DR Schubert</name></author><author><name sortKey="Finley, Kd" uniqKey="Finley K">KD Finley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wadhwa, R" uniqKey="Wadhwa R">R Wadhwa</name></author><author><name sortKey="Ryu, J" uniqKey="Ryu J">J Ryu</name></author><author><name sortKey="Gao, R" uniqKey="Gao R">R Gao</name></author><author><name sortKey="Choi, I K" uniqKey="Choi I">I-K Choi</name></author><author><name sortKey="Morrow, G" uniqKey="Morrow G">G Morrow</name></author><author><name sortKey="Kaur, K" uniqKey="Kaur K">K Kaur</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hewett, J" uniqKey="Hewett J">J Hewett</name></author><author><name sortKey="Ziefer, P" uniqKey="Ziefer P">P Ziefer</name></author><author><name sortKey="Bergeron, D" uniqKey="Bergeron D">D Bergeron</name></author><author><name sortKey="Naismith, T" uniqKey="Naismith T">T Naismith</name></author><author><name sortKey="Boston, H" uniqKey="Boston H">H Boston</name></author><author><name sortKey="Slater, D" uniqKey="Slater D">D Slater</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bragg, Dc" uniqKey="Bragg D">DC Bragg</name></author><author><name sortKey="Camp, Sm" uniqKey="Camp S">SM Camp</name></author><author><name sortKey="Kaufman, Ca" uniqKey="Kaufman C">CA Kaufman</name></author><author><name sortKey="Wilbur, Jd" uniqKey="Wilbur J">JD Wilbur</name></author><author><name sortKey="Boston, H" uniqKey="Boston H">H Boston</name></author><author><name sortKey="Schuback, De" uniqKey="Schuback D">DE Schuback</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bragg, Dc" uniqKey="Bragg D">DC Bragg</name></author><author><name sortKey="Kaufman, Ca" uniqKey="Kaufman C">CA Kaufman</name></author><author><name sortKey="Kock, N" uniqKey="Kock N">N Kock</name></author><author><name sortKey="Breakefield, Xo" uniqKey="Breakefield X">XO Breakefield</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bi, M" uniqKey="Bi M">M Bi</name></author><author><name sortKey="Naczki, C" uniqKey="Naczki C">C Naczki</name></author><author><name sortKey="Koritzinsky, M" uniqKey="Koritzinsky M">M Koritzinsky</name></author><author><name sortKey="Fels, D" uniqKey="Fels D">D Fels</name></author><author><name sortKey="Blais, J" uniqKey="Blais J">J Blais</name></author><author><name sortKey="Hu, N" uniqKey="Hu N">N Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Romero Ramirez, L" uniqKey="Romero Ramirez L">L Romero-Ramirez</name></author><author><name sortKey="Cao, H" uniqKey="Cao H">H Cao</name></author><author><name sortKey="Nelson, D" uniqKey="Nelson D">D Nelson</name></author><author><name sortKey="Hammond, E" uniqKey="Hammond E">E Hammond</name></author><author><name sortKey="Lee, A H" uniqKey="Lee A">A-H Lee</name></author><author><name sortKey="Yoshida, H" uniqKey="Yoshida H">H Yoshida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, P" uniqKey="Chen P">P Chen</name></author><author><name sortKey="Burdette, Aj" uniqKey="Burdette A">AJ Burdette</name></author><author><name sortKey="Porter, Jc" uniqKey="Porter J">JC Porter</name></author><author><name sortKey="Ricketts, Jc" uniqKey="Ricketts J">JC Ricketts</name></author><author><name sortKey="Fox, Sa" uniqKey="Fox S">SA Fox</name></author><author><name sortKey="Nery, Fc" uniqKey="Nery F">FC Nery</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Genomics</journal-id><journal-id journal-id-type="iso-abbrev">BMC Genomics</journal-id><journal-title-group><journal-title>BMC Genomics</journal-title></journal-title-group><issn pub-type="epub">1471-2164</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25903460</article-id><article-id pub-id-type="pmc">4415242</article-id><article-id pub-id-type="publisher-id">1518</article-id><article-id pub-id-type="doi">10.1186/s12864-015-1518-0</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>The pathogenic human Torsin A in <italic>Drosophila</italic> activates the unfolded protein response and increases susceptibility to oxidative stress</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Kim</surname><given-names>A-Young</given-names></name><address><email>kilenay@daum.net</email></address><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Seo</surname><given-names>Jong Bok</given-names></name><address><email>sjb@kbsi.re.kr</email></address><xref ref-type="aff" rid="Aff3"></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Won-tae</given-names></name><address><email>wtkim@korea.kr</email></address><xref ref-type="aff" rid="Aff4"></xref></contrib><contrib contrib-type="author"><name><surname>Choi</surname><given-names>Hee Jeong</given-names></name><address><email>chj52@snu.ac.kr</email></address><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Soo-Young</given-names></name><address><email>hl96022@daum.net</email></address><xref ref-type="aff" rid="Aff3"></xref></contrib><contrib contrib-type="author"><name><surname>Morrow</surname><given-names>Genevieve</given-names></name><address><email>Genevieve.Morrow@fmed.ulaval.ca</email></address><xref ref-type="aff" rid="Aff5"></xref></contrib><contrib contrib-type="author"><name><surname>Tanguay</surname><given-names>Robert M</given-names></name><address><email>robert.tanguay@ibis.ulaval.ca</email></address><xref ref-type="aff" rid="Aff5"></xref></contrib><contrib contrib-type="author"><name><surname>Steller</surname><given-names>Hermann</given-names></name><address><email>Hermann.Steller@rockefeller.edu</email></address><xref ref-type="aff" rid="Aff6"></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Koh</surname><given-names>Young Ho</given-names></name><address><email>kohyh@hallym.ac.kr</email></address><xref ref-type="aff" rid="Aff1"></xref><xref ref-type="aff" rid="Aff2"></xref></contrib><aff id="Aff1"><label></label>ILSONG Institute of Life Science, Hallym University, 1605-4 Gwanyangdong, Dongan-gu, Anyang, Gyeonggido 431-060 Republic of Korea</aff><aff id="Aff2"><label></label>Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do 200-702 Republic of Korea</aff><aff id="Aff3"><label></label>Korea Basic Science Institute, Sungbuk-gu, Seoul 136-713 Republic of Korea</aff><aff id="Aff4"><label></label>National Academy of Agricultural Science, Rural Development Administration, Suwon, 441-707 Republic of Korea</aff><aff id="Aff5"><label></label>Department of Molecular Biology, Medical Biochemistry & Pathology, Université Laval, Québec, Qc G1V 0A6 Canada</aff><aff id="Aff6"><label></label>Howard Hughes Medical Institute, the Rockefeller University, New York, NY 10065 USA</aff></contrib-group><pub-date pub-type="epub"><day>23</day><month>4</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>4</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2015</year></pub-date><volume>16</volume><issue>1</issue><elocation-id>338</elocation-id><history><date date-type="received"><day>13</day><month>9</month><year>2014</year></date><date date-type="accepted"><day>10</day><month>4</month><year>2015</year></date></history><permissions><copyright-statement>© Kim et al.; licensee BioMed Central. 2015</copyright-statement><license license-type="open-access"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p>Dystonia1 (DYT1) dystonia is caused by a glutamic acid deletion (ΔE) mutation in the gene encoding Torsin A in humans (HTorA). To investigate the unknown molecular and cellular mechanisms underlying DYT1 dystonia, we performed an unbiased proteomic analysis.</p></sec><sec><title>Results</title><p>We found that the amount of proteins and transcripts of an Endoplasmic reticulum (ER) resident chaperone Heat shock protein cognate 3 (HSC3) and a mitochondria chaperone Heat Shock Protein 22 (HSP22) were significantly increased in the HTorA<sup>ΔE</sup>– expressing brains compared to the normal HTorA (HTorA<sup>WT</sup>) expressing brains. The physiological consequences included an increased susceptibility to oxidative and ER stress compared to normal HTorA<sup>WT</sup> flies. The alteration of transcripts of Inositol-requiring enzyme-1 (IRE1)-dependent spliced X box binding protein 1(Xbp1), several ER chaperones, a nucleotide exchange factor, Autophagy related protein 8b (ATG8b) and components of the ER associated degradation (ERAD) pathway and increased expression of the Xbp1-enhanced Green Fluorescence Protein (eGFP) in HTorA<sup>ΔE</sup> brains strongly indicated the activation of the unfolded protein response (UPR). In addition, perturbed expression of the UPR sensors and inducers in the HTorA<sup>ΔE</sup><italic>Drosophila</italic> brains resulted in a significantly reduced life span of the flies. Furthermore, the types and quantities of proteins present in the anti-HSC3 positive microsomes in the HTorA<sup>ΔE</sup> brains were different from those of the HTorA<sup>WT</sup> brains.</p></sec><sec><title>Conclusion</title><p>Taken together, these data show that HTorA<sup>ΔE</sup> in <italic>Drosophila</italic> brains may activate the UPR and increase the expression of HSP22 to compensate for the toxic effects caused by HTorA<sup>ΔE</sup> in the brains.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/s12864-015-1518-0) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>DYT1 dystonia</kwd><kwd>Bip</kwd><kwd>HSC3</kwd><kwd>HSP22</kwd><kwd>Xbp1</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2015</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000230 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000230 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:4415242
|texte= The pathogenic human Torsin A in Drosophila activates the unfolded protein response and increases susceptibility to oxidative stress
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:25903460" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |