{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:28:07Z","timestamp":1793363287214,"version":"4.5.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer\u2019s disease, Huntington\u2019s disease and Parkinson\u2019s disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including\n                    <jats:italic>PARK7<\/jats:italic>\n                    which encodes the protein DJ-1 have been linked to early-onset, familial PD. In this regard, both PD of sporadic and genetic origins exhibit markers of ER stress-induced UPR. However, the relationship between pathogenic mutations in\n                    <jats:italic>PARK7<\/jats:italic>\n                    and ER stress-induced UPR in PD pathogenesis remains unclear. In most contexts, DJ-1 has been shown to protect against neuronal injury. However, we find that DJ-1 deficiency ameliorates death in the context of acute ER stress in vitro and in vivo. DJ-1 loss decreases protein and transcript levels of ATF4, a transcription factor critical to the ER response and reduces the levels of CHOP and BiP, its downstream effectors. The converse is observed with DJ-1 over-expression. Importantly, we find that over-expression of wild-type and PD-associated mutant form of\n                    <jats:italic>PARK7<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>L166P<\/jats:italic>\n                    <\/jats:sup>\n                    , enhances ER stress-induced neuronal death by regulating ATF4 transcription and translation. Our results demonstrate a previously unreported role for wild-type and mutant DJ-1 in the regulation of UPR and provides a potential link to PD pathogenesis.\n                  <\/jats:p>","DOI":"10.1038\/s41419-019-1354-2","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T07:05:57Z","timestamp":1549955157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["DJ-1 modulates the unfolded protein response and cell death via upregulation of ATF4 following ER stress"],"prefix":"10.1038","volume":"10","author":[{"given":"Jungwoo","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang Soo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace O.","family":"Iyirhiaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Marcogliese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve M.","family":"Callaghan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianbo","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth S.","family":"Slack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-3784","authenticated-orcid":false,"given":"David S.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"1354_CR1","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1056\/NEJM199810083391506","volume":"339","author":"AE Lang","year":"1998","unstructured":"Lang, A. E. & Lozano, A. M. Parkinson\u2019s disease. First of two parts. N. Engl. J. Med. 339, 1044\u20131053 (1998).","journal-title":"N. Engl. J. Med."},{"key":"1354_CR2","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1056\/NEJM199810153391607","volume":"339","author":"AE Lang","year":"1998","unstructured":"Lang, A. E. & Lozano, A. M. Parkinson\u2019s disease. Second of two parts. New Engl. J. Med. 339, 1130\u20131143 (1998).","journal-title":"New Engl. J. Med."},{"key":"1354_CR3","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","volume":"276","author":"MH Polymeropoulos","year":"1997","unstructured":"Polymeropoulos, M. H. et al. Mutation in the alpha-synuclein gene identified in families with Parkinson\u2019s disease. Science 276, 2045\u20132047 (1997).","journal-title":"Science"},{"key":"1354_CR4","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1111\/j.1468-1331.2004.00924.x","volume":"11","author":"EM Valente","year":"2004","unstructured":"Valente, E. M. et al. Identification of PINK1, the first mitochondrial gene causing Parkinson\u2019s disease. Eur. J. Neurol. 11, 366\u2013367 (2004).","journal-title":"Eur. J. Neurol."},{"key":"1354_CR5","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1093\/brain\/awh054","volume":"127","author":"R Bandopadhyay","year":"2004","unstructured":"Bandopadhyay, R. et al. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson\u2019s disease. Brain 127, 420\u2013430 (2004).","journal-title":"Brain"},{"key":"1354_CR6","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neulet.2007.08.010","volume":"425","author":"M Waragai","year":"2007","unstructured":"Waragai, M. et al. Plasma levels of DJ-1 as a possible marker for progression of sporadic Parkinson\u2019s disease. Neurosci. Lett. 425, 18\u201322 (2007).","journal-title":"Neurosci. Lett."},{"key":"1354_CR7","doi-asserted-by":"publisher","first-page":"10816","DOI":"10.1074\/jbc.M509079200","volume":"281","author":"J Choi","year":"2006","unstructured":"Choi, J. et al. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J. Biol. Chem. 281, 10816\u201310824 (2006).","journal-title":"J. Biol. Chem."},{"key":"1354_CR8","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s10072-003-0108-0","volume":"24","author":"V Bonifati","year":"2003","unstructured":"Bonifati, V. et al. DJ-1(PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurol. Sci. 24, 159\u2013160 (2003).","journal-title":"Neurol. Sci."},{"key":"1354_CR9","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.neulet.2008.12.053","volume":"452","author":"J Blackinton","year":"2009","unstructured":"Blackinton, J. et al. Post-transcriptional regulation of mRNA associated with DJ-1 in sporadic Parkinson disease. Neurosci. Lett. 452, 8\u201311 (2009).","journal-title":"Neurosci. Lett."},{"key":"1354_CR10","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/ana.10663","volume":"54","author":"S Hague","year":"2003","unstructured":"Hague, S. et al. Early-onset Parkinson\u2019s disease caused by a compound heterozygous DJ-1 mutation. Ann. Neurol. 54, 271\u2013274 (2003).","journal-title":"Ann. Neurol."},{"key":"1354_CR11","doi-asserted-by":"publisher","first-page":"15918","DOI":"10.1073\/pnas.1205102109","volume":"109","author":"MW Rousseaux","year":"2012","unstructured":"Rousseaux, M. W. et al. Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. Proc. Natl Acad. Sci. USA 109, 15918\u201315923 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1354_CR12","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1097\/NEN.0b013e3181efc01c","volume":"69","author":"J Vitte","year":"2010","unstructured":"Vitte, J. et al. Leucine-rich repeat kinase 2 is associated with the endoplasmic reticulum in dopaminergic neurons and accumulates in the core of Lewy bodies in Parkinson disease. J. Neuropathol. Exp. Neurol. 69, 959\u2013972 (2010).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"1354_CR13","doi-asserted-by":"publisher","first-page":"e22354","DOI":"10.1371\/journal.pone.0022354","volume":"6","author":"Y Yuan","year":"2011","unstructured":"Yuan, Y. et al. Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans. PLoS ONE 6, e22354 (2011).","journal-title":"PLoS ONE"},{"key":"1354_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.173","volume":"7","author":"I Celardo","year":"2016","unstructured":"Celardo, I. et al. Mitofusin-mediated ER stress triggers neurodegeneration in pink1\/parkin models of Parkinson\u2019s disease. Cell Death Dis. 7, e2271 (2016).","journal-title":"Cell Death Dis."},{"key":"1354_CR15","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.brainres.2016.04.042","volume":"1648","author":"G Mercado","year":"2016","unstructured":"Mercado, G., Castillo, V., Soto, P. & Sidhu, A. ER stress and Parkinson\u2019s disease: pathological inputs that converge into the secretory pathway. Brain Res. 1648, 626\u2013632 (2016).","journal-title":"Brain Res."},{"key":"1354_CR16","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.bbrc.2007.01.043","volume":"354","author":"JJ Hoozemans","year":"2007","unstructured":"Hoozemans, J. J. et al. Activation of the unfolded protein response in Parkinson\u2019s disease. Biochem. Biophys. Res. Commun. 354, 707\u2013711 (2007).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"1354_CR17","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1089\/ars.2014.5851","volume":"21","author":"SS Cao","year":"2014","unstructured":"Cao, S. S. & Kaufman, R. J. Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease. Antioxid. Redox Signal. 21, 396\u2013413 (2014).","journal-title":"Antioxid. Redox Signal."},{"key":"1354_CR18","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1523\/JNEUROSCI.2292-12.2013","volume":"33","author":"X Sun","year":"2013","unstructured":"Sun, X. et al. ATF4 protects against neuronal death in cellular Parkinson\u2019s disease models by maintaining levels of parkin. J. Neurosci. 33, 2398\u20132407 (2013).","journal-title":"J. Neurosci."},{"key":"1354_CR19","doi-asserted-by":"publisher","first-page":"11269","DOI":"10.1073\/pnas.0400541101","volume":"101","author":"KM Vattem","year":"2004","unstructured":"Vattem, K. M. & Wek, R. C. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc. Natl Acad. Sci. USA 101, 11269\u201311274 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1354_CR20","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.neulet.2016.05.039","volume":"627","author":"JC Gully","year":"2016","unstructured":"Gully, J. C. et al. Up-regulation of activating transcription factor 4 induces severe loss of dopamine nigral neurons in a rat model of Parkinson\u2019s disease. Neurosci. Lett. 627, 36\u201341 (2016).","journal-title":"Neurosci. Lett."},{"key":"1354_CR21","doi-asserted-by":"publisher","first-page":"4998","DOI":"10.1096\/fj.13-236075","volume":"27","author":"J Yang","year":"2013","unstructured":"Yang, J. et al. Translational up-regulation of polycystic kidney disease protein PKD2 by endoplasmic reticulum stress. FASEB J. 27, 4998\u20135009 (2013).","journal-title":"FASEB J."},{"key":"1354_CR22","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.biocel.2007.01.020","volume":"40","author":"K Ameri","year":"2008","unstructured":"Ameri, K. & Harris, A. L. Activating transcription factor 4. Int. J. Biochem. Cell. Biol. 40, 14\u201321 (2008).","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"1354_CR23","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrm2199","volume":"8","author":"D Ron","year":"2007","unstructured":"Ron, D. & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell. Biol. 8, 519\u2013529 (2007).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"1354_CR24","doi-asserted-by":"publisher","first-page":"37375","DOI":"10.1074\/jbc.M303619200","volume":"278","author":"S Luo","year":"2003","unstructured":"Luo, S., Baumeister, P., Yang, S., Abcouwer, S. F. & Lee, A. S. Induction of Grp78\/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF\/CRE site independent of the endoplasmic reticulum stress elements. J. Biol. Chem. 278, 37375\u201337385 (2003).","journal-title":"J. Biol. Chem."},{"key":"1354_CR25","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1242\/jcs.127340","volume":"126","author":"E Duplan","year":"2013","unstructured":"Duplan, E. et al. 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. J. Cell Sci. 126, 2124\u20132133 (2013).","journal-title":"J. Cell Sci."},{"key":"1354_CR26","doi-asserted-by":"publisher","first-page":"10244","DOI":"10.1073\/pnas.0708518105","volume":"105","author":"MP van der Brug","year":"2008","unstructured":"van der Brug, M. P. et al. RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways. Proc. Natl Acad. Sci. USA 105, 10244\u201310249 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1354_CR27","doi-asserted-by":"publisher","first-page":"683920","DOI":"10.1155\/2013\/683920","volume":"2013","author":"H Ariga","year":"2013","unstructured":"Ariga, H. et al. Neuroprotective function of DJ-1 in Parkinson\u2019s disease. Oxid. Med. Cell. Longev. 2013, 683920 (2013).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"1354_CR28","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/jcp.1040760202","volume":"76","author":"RP Perry","year":"1970","unstructured":"Perry, R. P. & Kelley, D. E. Inhibition of RNA synthesis by actinomycin D: characteristic dose-response of different RNA species. J. Cell. Physiol. 76, 127\u2013139 (1970).","journal-title":"J. Cell. Physiol."},{"key":"1354_CR29","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55\u201363 (1983).","journal-title":"J. Immunol. Methods"},{"key":"1354_CR30","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","volume":"6","author":"AG Porter","year":"1999","unstructured":"Porter, A. G. & Janicke, R. U. Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6, 99\u2013104 (1999).","journal-title":"Cell Death Differ"},{"key":"1354_CR31","doi-asserted-by":"publisher","first-page":"3186","DOI":"10.1073\/pnas.0914876107","volume":"107","author":"H Aleyasin","year":"2010","unstructured":"Aleyasin, H. et al. DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway. Proc. Natl Acad. Sci. USA 107, 3186\u20133191 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1354_CR32","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/sj.embor.7400074","volume":"5","author":"T Taira","year":"2004","unstructured":"Taira, T. et al. DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep. 5, 213\u2013218 (2004).","journal-title":"EMBO Rep."},{"key":"1354_CR33","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/cdd.2010.142","volume":"18","author":"L Bouman","year":"2011","unstructured":"Bouman, L. et al. Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress. Cell Death Differ 18, 769\u2013782 (2011).","journal-title":"Cell Death Differ"},{"key":"1354_CR34","doi-asserted-by":"publisher","first-page":"16938","DOI":"10.1523\/JNEUROSCI.1598-10.2010","volume":"30","author":"Z Galehdar","year":"2010","unstructured":"Galehdar, Z. et al. Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J. Neurosci. 30, 16938\u201316948 (2010).","journal-title":"J. Neurosci."},{"key":"1354_CR35","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/S0092-8674(01)00568-2","volume":"107","author":"V Brown","year":"2001","unstructured":"Brown, V. et al. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107, 477\u2013487 (2001).","journal-title":"Cell"},{"key":"1354_CR36","doi-asserted-by":"publisher","first-page":"2987","DOI":"10.1073\/pnas.0306453101","volume":"101","author":"I Lopez de Silanes","year":"2004","unstructured":"Lopez de Silanes, I., Zhan, M., Lal, A., Yang, X. & Gorospe, M. Identification of a target RNA motif for RNA-binding protein HuR. Proc. Natl Acad. Sci. USA 101, 2987\u20132992 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1354_CR37","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/nrm1618","volume":"6","author":"M Holcik","year":"2005","unstructured":"Holcik, M. & Sonenberg, N. Translational control in stress and apoptosis. Nat. Rev. Mol. Cell. Biol. 6, 318\u2013327 (2005).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"1354_CR38","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1111\/j.1471-4159.2003.02265.x","volume":"87","author":"DJ Moore","year":"2003","unstructured":"Moore, D. J., Zhang, L., Dawson, T. M. & Dawson, V. L. A missense mutation (L166P) in DJ-1, linked to familial Parkinson\u2019s disease, confers reduced protein stability and impairs homo-oligomerization. J. Neurochem. 87, 1558\u20131567 (2003).","journal-title":"J. Neurochem."},{"key":"1354_CR39","doi-asserted-by":"publisher","first-page":"36588","DOI":"10.1074\/jbc.M304272200","volume":"278","author":"DW Miller","year":"2003","unstructured":"Miller, D. W. et al. L166P mutant DJ-1, causative for recessive Parkinson\u2019s disease, is degraded through the ubiquitin-proteasome system. J. Biol. Chem. 278, 36588\u201336595 (2003).","journal-title":"J. Biol. Chem."},{"key":"1354_CR40","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/cdd.2008.169","volume":"16","author":"S Zucchelli","year":"2009","unstructured":"Zucchelli, S. et al. Aggresome-forming TTRAP mediates pro-apoptotic properties of Parkinson\u2019s disease-associated DJ-1 missense mutations. Cell Death Differ 16, 428\u2013438 (2009).","journal-title":"Cell Death Differ"},{"key":"1354_CR41","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1750-1326-7-40","volume":"7","author":"H Ren","year":"2012","unstructured":"Ren, H., Fu, K., Mu, C., Zhen, X. & Wang, G. L166P mutant DJ-1 promotes cell death by dissociating Bax from mitochondrial Bcl-XL. Mol. Neurodegener. 7, 40 (2012).","journal-title":"Mol. Neurodegener."},{"key":"1354_CR42","doi-asserted-by":"publisher","first-page":"e106601","DOI":"10.1371\/journal.pone.0106601","volume":"9","author":"M Parsanejad","year":"2014","unstructured":"Parsanejad, M. et al. DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress. PLoS ONE 9, e106601 (2014).","journal-title":"PLoS ONE"},{"key":"1354_CR43","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nchembio782","volume":"2","author":"DA Bosco","year":"2006","unstructured":"Bosco, D. A. et al. Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization. Nat. Chem. Biol. 2, 249\u2013253 (2006).","journal-title":"Nat. Chem. Biol."},{"key":"1354_CR44","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1002\/jnr.21191","volume":"85","author":"Y Nakabeppu","year":"2007","unstructured":"Nakabeppu, Y., Tsuchimoto, D., Yamaguchi, H. & Sakumi, K. Oxidative damage in nucleic acids and Parkinson\u2019s disease. J. Neurosci. Res 85, 919\u2013934 (2007).","journal-title":"J. Neurosci. Res"},{"key":"1354_CR45","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1046\/j.1471-4159.1998.70010268.x","volume":"70","author":"E Floor","year":"1998","unstructured":"Floor, E. & Wetzel, M. G. Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J. Neurochem. 70, 268\u2013275 (1998).","journal-title":"J. Neurochem."},{"key":"1354_CR46","doi-asserted-by":"publisher","first-page":"e54087","DOI":"10.1371\/journal.pone.0054087","volume":"8","author":"C Maita","year":"2013","unstructured":"Maita, C., Maita, H., Iguchi-Ariga, S. M. & Ariga, H. Monomer DJ-1 and its N-terminal sequence are necessary for mitochondrial localization of DJ-1 mutants. PLoS ONE 8, e54087 (2013).","journal-title":"PLoS ONE"},{"key":"1354_CR47","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1600-0404.1989.tb01780.x","volume":"126","author":"JW Tetrud","year":"1989","unstructured":"Tetrud, J. W. & Langston, J. W. MPTP-induced parkinsonism as a model for Parkinson\u2019s disease. Acta Neurol. Scand. Suppl. 126, 35\u201340 (1989).","journal-title":"Acta Neurol. Scand. Suppl."},{"key":"1354_CR48","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1007\/s12640-013-9375-6","volume":"24","author":"Y Huang","year":"2013","unstructured":"Huang, Y. et al. RESP18 is involved in the cytotoxicity of dopaminergic neurotoxins in MN9D cells. Neurotox. Res. 24, 164\u2013175 (2013).","journal-title":"Neurotox. Res."},{"key":"1354_CR49","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1126\/science.286.5445.1735","volume":"286","author":"P Bouillet","year":"1999","unstructured":"Bouillet, P. et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286, 1735\u20131738 (1999).","journal-title":"Science"},{"key":"1354_CR50","doi-asserted-by":"publisher","first-page":"7860","DOI":"10.1523\/JNEUROSCI.19-18-07860.1999","volume":"19","author":"SP Cregan","year":"1999","unstructured":"Cregan, S. P. et al. Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons. J. Neurosci. 19, 7860\u20137869 (1999).","journal-title":"J. Neurosci."},{"key":"1354_CR51","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1083\/jcb.200105137","volume":"155","author":"A Fortin","year":"2001","unstructured":"Fortin, A. et al. APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell death. J. Cell. Biol. 155, 207\u2013216 (2001).","journal-title":"J. Cell. Biol."},{"key":"1354_CR52","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1182\/blood.V99.3.736","volume":"99","author":"HC Masuoka","year":"2002","unstructured":"Masuoka, H. C. & Townes, T. M. Targeted disruption of the activating transcription factor 4 gene results in severe fetal anemia in mice. Blood 99, 736\u2013745 (2002).","journal-title":"Blood"},{"key":"1354_CR53","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1126\/science.1090072","volume":"302","author":"A Villunger","year":"2003","unstructured":"Villunger, A. et al. p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 302, 1036\u20131038 (2003).","journal-title":"Science"},{"key":"1354_CR54","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1073\/pnas.95.5.2509","volume":"95","author":"TC He","year":"1998","unstructured":"He, T. C. et al. A simplified system for generating recombinant adenoviruses. Proc. Natl Acad. Sci. USA 95, 2509\u20132514 (1998).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1354_CR55","doi-asserted-by":"publisher","first-page":"23162","DOI":"10.1074\/jbc.M112.346437","volume":"287","author":"ME Haque","year":"2012","unstructured":"Haque, M. E. et al. Inactivation of Pink1 gene in vivo sensitizes dopamine-producing neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and can be rescued by autosomal recessive Parkinson disease genes, Parkin or DJ-1. J. Biol. Chem. 287, 23162\u201323170 (2012).","journal-title":"J. Biol. Chem."},{"key":"1354_CR56","doi-asserted-by":"publisher","first-page":"5215","DOI":"10.1073\/pnas.0501282102","volume":"102","author":"RH Kim","year":"2005","unstructured":"Kim, R. H. et al. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc. Natl Acad. Sci. USA 102, 5215\u20135220 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1354_CR57","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1083\/jcb.200202130","volume":"158","author":"SP Cregan","year":"2002","unstructured":"Cregan, S. P. et al. Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death. J. Cell. Biol. 158, 507\u2013517 (2002).","journal-title":"J. Cell. Biol."},{"key":"1354_CR58","first-page":"21","volume":"Chapter 3","author":"C Fasano","year":"2008","unstructured":"Fasano, C., Thibault, D. & Trudeau, L. E. Culture of postnatal mesencephalic dopamine neurons on an astrocyte monolayer. Curr. Protoc. Neurosci. Chapter 3, 21 (2008).","journal-title":"Curr. Protoc. Neurosci."},{"key":"1354_CR59","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.ccr.2005.02.010","volume":"7","author":"RH Kim","year":"2005","unstructured":"Kim, R. H. et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 7, 263\u2013273 (2005).","journal-title":"Cancer Cell"},{"key":"1354_CR60","doi-asserted-by":"publisher","first-page":"3254","DOI":"10.1093\/hmg\/ddn221","volume":"17","author":"G Liang","year":"2008","unstructured":"Liang, G. et al. Polycystin-2 down-regulates cell proliferation via promoting PERK-dependent phosphorylation of eIF2alpha. Hum. Mol. Genet. 17, 3254\u20133262 (2008).","journal-title":"Hum. Mol. Genet."}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-019-1354-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-019-1354-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-019-1354-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T11:31:21Z","timestamp":1671190281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-019-1354-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,12]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["1354"],"URL":"https:\/\/doi.org\/10.1038\/s41419-019-1354-2","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,12]]},"assertion":[{"value":"17 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"135"}}