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W2005917373 abstract "Loss-of-function mutation in the DJ-1 gene causes a subset of familial Parkinson disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. DJ-1 has multiple functions, including transcriptional regulation, and one of transcriptional target genes for DJ-1 is the tyrosine hydroxylase (TH) gene, the product of which is a key enzyme for dopamine biosynthesis. It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. In this study, we found that knockdown of human DJ-1 by small interference RNA in human dopaminergic cell lines attenuated TH gene expression and 4-dihydroxy-l-phenylalanine production but that knockdown or knock-out of mouse DJ-1 in mouse cell lines or in mice did not affect such expression and TH activity. In reporter assays using the human TH gene promoter linked to the luciferase gene, stimulation of TH promoter activity was observed in human cells, but not mouse cells, that had been transfected with DJ-1. Although human DJ-1 and mouse DJ-1 were associated either with human or with mouse PSF, TH promoter activity inhibited by PSF was restored by human DJ-1 but not by mouse DJ-1. Chromatin immunoprecipitation assays revealed that the complex of PSF with DJ-1 bound to the human but not the mouse TH gene promoter. These results suggest a novel species-specific transcriptional regulation of the TH promoter by DJ-1 and one of the mechanisms for no reduction of TH in DJ-1-knock-out mice. Loss-of-function mutation in the DJ-1 gene causes a subset of familial Parkinson disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. DJ-1 has multiple functions, including transcriptional regulation, and one of transcriptional target genes for DJ-1 is the tyrosine hydroxylase (TH) gene, the product of which is a key enzyme for dopamine biosynthesis. It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter. In this study, we found that knockdown of human DJ-1 by small interference RNA in human dopaminergic cell lines attenuated TH gene expression and 4-dihydroxy-l-phenylalanine production but that knockdown or knock-out of mouse DJ-1 in mouse cell lines or in mice did not affect such expression and TH activity. In reporter assays using the human TH gene promoter linked to the luciferase gene, stimulation of TH promoter activity was observed in human cells, but not mouse cells, that had been transfected with DJ-1. Although human DJ-1 and mouse DJ-1 were associated either with human or with mouse PSF, TH promoter activity inhibited by PSF was restored by human DJ-1 but not by mouse DJ-1. Chromatin immunoprecipitation assays revealed that the complex of PSF with DJ-1 bound to the human but not the mouse TH gene promoter. These results suggest a novel species-specific transcriptional regulation of the TH promoter by DJ-1 and one of the mechanisms for no reduction of TH in DJ-1-knock-out mice. IntroductionParkinson disease (PD) 3The abbreviations used are: PDParkinson diseaseTHtyrosine hydroxylasehTHhuman THmTHmouse THl-DOPA4-dihydroxy-l-phenylalaninePSFpolypyrimidine tract-binding protein-associated splicing factor. is the most common movement disorder caused by gradual loss of dopaminergic neurons in the substantia nigra pars compacta. Although most cases are sporadic, 5–10% of PD patients carry mutations with a Mendelian inheritance, and mutations in parkin, DJ-1, and PINK1 genes have been linked to autosomal recessive forms of PD (1Kitada T. Asakawa S. Hattori N. Matsumine H. Yamamura Y. Minoshima S. Yokochi M. Mizuno Y. Shimizu N. Nature. 1998; 392: 605-608Crossref PubMed Scopus (4123) Google Scholar, 2Bonifati V. Rizzu P. van Baren M.J. Schaap O. Breedveld G.J. Krieger E. Dekker M.C. Squitieri F. Ibanez P. Joosse M. van Dongen J.W. Vanacore N. van Swieten J.C. Brice A. Meco G. van Duijn C.M. Oostra B.A. Heutink P. Science. 2003; 299: 256-259Crossref PubMed Scopus (2195) Google Scholar, 3Valente E.M. Abou-Sleiman P.M. Caputo V. Muqit M.M. Harvey K. Gispert S. Ali Z. Del Turco D. Bentivoglio A.R. Healy D.G. Albanese A. Nussbaum R. González-Maldonado R. Deller T. Salvi S. Cortelli P. Gilks W.P. Latchman D.S. Harvey R.J. Dallapiccola B. Auburger G. Wood N.W. Science. 2004; 304: 1158-1160Crossref PubMed Scopus (2630) Google Scholar). Although a large number of studies have been carried out to determine whether inactivation of each of these genes in mice or fruit flies results in progressive and selective loss of dopaminergic neurons, almost all of the studies, including studies using mice with single or triple deficiency in parkin, DJ-1, and PINK1 genes, showed no loss of dopaminergic neurons in the substantia nigra pars compacta (4Goldberg M.S. Fleming S.M. Palacino J.J. Cepeda C. Lam H.A. Bhatnagar A. Meloni E.G. Wu N. Ackerson L.C. Klapstein G.J. Gajendiran M. Roth B.L. Chesselet M.F. Maidment N.T. Levine M.S. Shen J. J. Biol. Chem. 2003; 278: 43628-43635Abstract Full Text Full Text PDF PubMed Scopus (714) Google Scholar, 5Goldberg M.S. Pisani A. Haburcak M. Vortherms T.A. Kitada T. Costa C. Tong Y. Martella G. Tscherter A. Martins A. Bernardi G. Roth B.L. Pothos E.N. Calabresi P. Shen J. Neuron. 2005; 45: 489-496Abstract Full Text Full Text PDF PubMed Scopus (435) Google Scholar, 6Itier J.M. Ibanez P. Mena M.A. Abbas N. Cohen-Salmon C. Bohme G.A. Laville M. Pratt J. Corti O. Pradier L. Ret G. Joubert C. Periquet M. Araujo F. Negroni J. Casarejos M.J. Canals S. Solano R. Serrano A. Gallego E. Sanchez M. Denefle P. Benavides J. Tremp G. Rooney T.A. Brice A. Garcia de Yebenes J. Hum. Mol. Genet. 2003; 12: 2277-2291Crossref PubMed Scopus (439) Google Scholar, 7Pesah Y. Pham T. Burgess H. Middlebrooks B. Verstreken P. Zhou Y. Harding M. Bellen H. Mardon G. Development. 2004; 131: 2183-2194Crossref PubMed Scopus (366) Google Scholar, 8Perez F.A. Palmiter R.D. Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 2174-2179Crossref PubMed Scopus (357) Google Scholar, 9Andres-Mateos E. Perier C. Zhang L. Blanchard-Fillion B. Greco T.M. Thomas B. Ko H.S. Sasaki M. Ischiropoulos H. Przedborski S. Dawson T.M. Dawson V.L. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 14807-14812Crossref PubMed Scopus (385) Google Scholar, 10Görner K. Holtorf E. Waak J. Pham T.T. Vogt-Weisenhorn D.M. Wurst W. Haass C. Kahle P.J. J. Biol. Chem. 2007; 282: 13680-13691Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 11Kitada T. Pisani A. Porter D.R. Yamaguchi H. Tscherter A. Martella G. Bonsi P. Zhang C. Pothos E.N. Shen J. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 11441-11446Crossref PubMed Scopus (403) Google Scholar, 12Wood-Kaczmar A. Gandhi S. Yao Z. Abramov A.Y. Miljan E.A. Keen G. Stanyer L. Hargreaves I. Klupsch K. Deas E. Downward J. Mansfield L. Jat P. Taylor J. Heales S. Duchen M.R. Latchman D. Tabrizi S.J. Wood N.W. PLoS ONE. 2008; 3: e2455Crossref PubMed Scopus (262) Google Scholar).DJ-1 was first identified by our group as a novel oncogene that transformed mouse NIH3T3 cells in cooperation with activated H-ras (13Nagakubo D. Taira T. Kitaura H. Ikeda M. Tamai K. Iguchi-Ariga S.M. Ariga H. Biochem. Biophys. Res. Commun. 1997; 231: 509-513Crossref PubMed Scopus (660) Google Scholar). Deletion and point (L166P) mutations of DJ-1 have been shown to be responsible for the onset of familial Parkinson disease, PARK7 (2Bonifati V. Rizzu P. van Baren M.J. Schaap O. Breedveld G.J. Krieger E. Dekker M.C. Squitieri F. Ibanez P. Joosse M. van Dongen J.W. Vanacore N. van Swieten J.C. Brice A. Meco G. van Duijn C.M. Oostra B.A. Heutink P. Science. 2003; 299: 256-259Crossref PubMed Scopus (2195) Google Scholar), and other homozygous and heterozygous mutations of DJ-1 have been identified in patients with familial or sporadic PD (14Abou-Sleiman P.M. Healy D.G. Quinn N. Lees A.J. Wood N.W. Ann. Neurol. 2003; 54: 283-286Crossref PubMed Scopus (319) Google Scholar, 15Hague S. Rogaeva E. Hernandez D. Gulick C. Singleton A. Hanson M. Johnson J. Weiser R. Gallardo M. Ravina B. Gwinn-Hardy K. Crawley A. St. George-Hyslop P.H. Lang A.E. Heutink P. Bonifati V. Hardy J. Singleton A. Ann. Neurol. 2003; 54: 271-274Crossref PubMed Scopus (206) Google Scholar, 16Hedrich K. Djarmati A. Schäfer N. Hering R. Wellenbrock C. Weiss P.H. Hilker R. Vieregge P. Ozelius L.J. Heutink P. Bonifati V. Schwinger E. Lang A.E. Noth J. Bressman S.B. Pramstaller P.P. Riess O. Klein C. Neurology. 2004; 62: 389-394Crossref PubMed Scopus (176) Google Scholar). DJ-1 is a multifunctional protein and plays roles in transcriptional regulation (17Takahashi K. Taira T. Niki T. Seino C. Iguchi-Ariga S.M. Ariga H. J. Biol. Chem. 2001; 276: 37556-37563Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar, 18Niki T. Takahashi-Niki K. Taira T. Iguchi-Ariga S.M. Ariga H. Mol. Cancer Res. 2003; 1: 247-261PubMed Google Scholar, 19Shinbo Y. Taira T. Niki T. Iguchi-Ariga S.M. Ariga H. Int. J. Oncol. 2005; 26: 641-648PubMed Google Scholar, 20Zhong N. Kim C.Y. Rizzu P. Geula C. Porter D.R. Pothos E.N. Squitieri F. Heutink P. Xu J. J. Biol. Chem. 2006; 281: 20940-20948Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 21Clements C.M. McNally R.S. Conti B.J. Mak T.W. Ting J.P. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 15091-15096Crossref PubMed Scopus (636) Google Scholar, 22Tillman J.E. Yuan J. Gu G. Fazli L. Ghosh R. Flynt A.S. Gleave M. Rennie P.S. Kasper S. Cancer Res. 2007; 67: 4630-4637Crossref PubMed Scopus (84) Google Scholar, 23Ishikawa S. Taira T. Niki T. Takahashi-Niki K. Maita C. Maita H. Ariga H. Iguchi-Ariga S.M. J. Biol. Chem. 2009; 284: 28832-28844Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 24Fan J. Ren H. Jia N. Fei E. Zhou T. Jiang P. Wu M. Wang G. J. Biol. Chem. 2008; 283: 4022-4030Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar, 25Xu J. Zhong N. Wang H. Elias J.E. Kim C.Y. Woldman I. Pifl C. Gygi S.P. Geula C. Yankner B.A. Hum. Mol. Genet. 2005; 14: 1231-1241Crossref PubMed Scopus (220) Google Scholar) and antioxidative stress function (26Canet-Avilés R.M. Wilson M.A. Miller D.W. Ahmad R. McLendon C. Bandyopadhyay S. Baptista M.J. Ringe D. Petsko G.A. Cookson M.R. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 9103-9108Crossref PubMed Scopus (894) Google Scholar, 27Taira T. Saito Y. Niki T. Iguchi-Ariga S.M. Takahashi K. Ariga H. EMBO Rep. 2004; 5: 213-218Crossref PubMed Scopus (734) Google Scholar, 28Kinumi T. Kimata J. Taira T. Ariga H. Niki E. Biochem. Biophys. Res. Commun. 2004; 317: 722-728Crossref PubMed Scopus (299) Google Scholar, 29Martinat C. Shendelman S. Jonason A. Leete T. Beal M.F. Yang L. Floss T. Abeliovich A. PLoS Biol. 2004; 2: e327Crossref PubMed Scopus (242) Google Scholar, 30Inden M. Taira T. Kitamura Y. Yanagida T. Tsuchiya D. Takata K. Yanagisawa D. Nishimura K. Taniguchi T. Kiso Y. Yoshimoto K. Agatsuma T. Koide-Yoshida S. Iguchi-Ariga S.M. Shimohama S. Ariga H. Neurobiol. Dis. 2006; 24: 144-158Crossref PubMed Scopus (167) Google Scholar, 31Yanagida T. Tsushima J. Kitamura Y. Yanagisawa D. Takata K. Shibaike T. Yamamoto A. Taniguchi T. Yasui H. Taira T. Morikawa S. Inubushi T. Tooyama I. Ariga H. Oxid. Med. Cell. Longev. 2009; 2: 36-42Crossref PubMed Scopus (66) Google Scholar), and loss of its functions leads to the onset of Parkinson disease and cancer. Although DJ-1 does not directly bind to DNA, DJ-1 acts as a co-activator to activate various transcription factors, including the androgen receptor, p53, PSF, and Nrf2, by sequestering their inhibitory factors (17Takahashi K. Taira T. Niki T. Seino C. Iguchi-Ariga S.M. Ariga H. J. Biol. Chem. 2001; 276: 37556-37563Abstract Full Text Full Text PDF PubMed Scopus (287) Google Scholar, 18Niki T. Takahashi-Niki K. Taira T. Iguchi-Ariga S.M. Ariga H. Mol. Cancer Res. 2003; 1: 247-261PubMed Google Scholar, 19Shinbo Y. Taira T. Niki T. Iguchi-Ariga S.M. Ariga H. Int. J. Oncol. 2005; 26: 641-648PubMed Google Scholar, 20Zhong N. Kim C.Y. Rizzu P. Geula C. Porter D.R. Pothos E.N. Squitieri F. Heutink P. Xu J. J. Biol. Chem. 2006; 281: 20940-20948Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 21Clements C.M. McNally R.S. Conti B.J. Mak T.W. Ting J.P. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 15091-15096Crossref PubMed Scopus (636) Google Scholar).Dopamine is synthesized by two steps as follows. Tyrosine is converted to l-DOPA by tyrosine hydroxylase (TH), and l-DOPA is then converted to dopamine by l-DOPA decarboxylase. TH is, therefore, a key enzyme for dopamine biosynthesis and is used as a marker for dopaminergic neurons. It has been reported that PSF, a transcription co-repressor, binds to the promoter region of the TH gene to repress its expression and that human DJ-1 binds to PSF to sequester the PSF·co-repressor complex, leading to activation of TH gene expression in cultured human cells (20Zhong N. Kim C.Y. Rizzu P. Geula C. Porter D.R. Pothos E.N. Squitieri F. Heutink P. Xu J. J. Biol. Chem. 2006; 281: 20940-20948Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar). In addition to transcriptional activation of the TH gene by DJ-1, we have reported that DJ-1 activated TH and l-DOPA decarboxylase through direct binding to TH and l-DOPA decarboxylase in an oxidative status of DJ-1-dependent manner (23Ishikawa S. Taira T. Niki T. Takahashi-Niki K. Maita C. Maita H. Ariga H. Iguchi-Ariga S.M. J. Biol. Chem. 2009; 284: 28832-28844Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar). Although human DJ-1 activates TH gene expression in cultured human dopaminergic cells, the reason why knock-out of DJ-1 expression did not affect the dopamine level in mice is not known.In this study, we compared the roles of human DJ-1 and mouse DJ-1 in expression of the TH gene, and we found that DJ-1 activates TH expression at the transcriptional level in human cells but not in mouse cells due to loss of PSF·DJ-1 binding to the mouse TH gene, suggesting different regulatory systems of the TH gene by DJ-1 in humans and mice.DISCUSSIONIn this study, we found that expression of the TH gene and TH activity were reduced in DJ-1-knockdown human cells but not in DJ-1-knockdown or DJ-1-knock-out mouse cells and that this occurred at the transcriptional level, where PSF, a transcription co-repressor, was sequestered from the promoter region by DJ-1 in human cells. Although mouse DJ-1 was associated with mouse PSF, ChIP assays showed that the recognition sequence was absent in the mouse TH promoter, meaning that there was no repression of TH gene expression by PSF in mouse cells. These findings indicate a species-specific regulation of TH gene expression by DJ-1 and PSF. It has been reported that PSF binds to the promoter region of the TH gene to repress its expression and that human DJ-1 binds to PSF to sequester the PSF·co-repressor complex, leading to activation of TH gene expression in cultured human cells (36Meulener M. Whitworth A.J. Armstrong-Gold C.E. Rizzu P. Heutink P. Wes P.D. Pallanck L.J. Bonini N.M. Curr. Biol. 2005; 15: 1572-1577Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar). In DJ-1-knock-out mice, however, no severe phenotype, including loss of dopamine, has been reported (13Nagakubo D. Taira T. Kitaura H. Ikeda M. Tamai K. Iguchi-Ariga S.M. Ariga H. Biochem. Biophys. Res. Commun. 1997; 231: 509-513Crossref PubMed Scopus (660) Google Scholar, 37Kim R.H. Smith P.D. Aleyasin H. Hayley S. Mount M.P. Pownall S. Wakeham A. You-Ten A.J. Kalia S.K. Horne P. Westaway D. Lozano A.M. Anisman H. Park D.S. Mak T.W. Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 5215-5220Crossref PubMed Scopus (576) Google Scholar, 38Chen L. Cagniard B. Mathews T. Jones S. Koh H.C. Ding Y. Carvey P.M. Ling Z. Kang U.J. Zhuang X. J. Biol. Chem. 2005; 280: 21418-21426Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). Our study, therefore, shows one reason for no loss of dopamine in DJ-1-knock-out mice.In reporter assays using luciferase gene-linked promoters from human and mouse TH genes, stimulation of TH promoter activity by DJ-1 was observed in the homologous combination between the human TH promoter, human DJ-1, and human cells but not between human TH promoter, human DJ-1, and mouse cells or between mouse TH promoter, mouse DJ-1, and mouse cells. Furthermore, stimulation of human TH promoter activity by human DJ-1 was specific to dopaminergic cells (Fig. 3). Luciferase activity in mouse Neuro-2a cells was higher than that in human SH-SY5Y cells (supplemental Fig. 1). The expression levels of DJ-1 in Neuro-2a and SH-SY5Y cells are similar. Because transfection efficiency of plasmid DNA in Neuro-2a cells is higher than that in SH-SY5Y cells, it is thought that high luciferase activity in Neuro-2a cells was obtained due to different transfection efficiency. Expression levels of endogenous DJ-1 in all of the cells are at a similar level (Fig. 3E), and luciferase activity corresponding to the human TH promoter was stimulated by transfected FLAG-human DJ-1 in a dose-dependent manner (Fig. 3, A and B). Because two plasmid DNAs, expression vectors for luciferase and FLAG-DJ-1, are generally transfected into the same cell at high frequency, luciferase activities obtained are thought to be responses to transfected FLAG-DJ-1 but not to endogenous DJ-1. Although it has been reported that PSF binds to the region spanning −2909 to −2707 upstream of the transcriptional start site to repress expression of the human TH gene, the DNA-binding sequence of PSF has not yet been determined. Because the identity of amino acid sequences between human and mouse PSFs is 93.51% and because we showed that both human DJ-1 and mouse DJ-1 bind to human PSF and that human and mouse PSF bind to each other (Fig. 4), human and mouse DJ-1s have a potential activity to bind to PSF of any mammalian species. Since we identified DJ-1 in 1997, we have been examining the DNA binding activity of DJ-1. No binding activity of DJ-1 was observed until now, and this study showed that DJ-1 directly binds to PSF, suggesting that DJ-1 binds to DNA via PSF. The results also show that mouse DJ-1 possessing binding activity to human PSF did not activate the human TH promoter in human SH-SY5Y cells. If sequestration of human PSF from the human TH gene promoter by DJ-1 is critical for TH gene expression, mouse DJ-1 seems to have some effect on TH gene expression. We do not have a clear answer to this point at present. Because the identity of amino acid sequences between human DJ-1 and mouse DJ-1 is 97%, there seem to be some structural/conformational differences between the two proteins. Because transcriptional activation or repression requires a proper complex comprised of multiple proteins, some structural/conformational differences may affect the regulation of gene expression. The identity of nucleotide sequences of the region corresponding to −2909 to −2707 between human and mouse TH genes is 44.29%. Furthermore, we found that DJ-1·PSF complex bound to the region spanning −2829 to −2790 in the human TH promoter (Fig. 8). Although the PSF-DNA binding sequence has not been determined, knockdown and knock-out of PSF and DJ-1 expression in mouse cells and in primary neuron culture, respectively, did not affect mouse TH gene expression, and no binding of DJ-1·PSF complex in this region was found in mouse cells (Fig. 6). Furthermore, competitive stimulation of human but not mouse TH promoter activity that had been inhibited by PSF was restored by DJ-1 (Fig. 5). DNA binding activity of PSF was attenuated by DJ-1 in a dose-dependent manner (Fig. 7). DJ-1-stimulated activity of human TH promoter with the region spanning −2829 to −2790 deleted was lower than that of human TH promoter without the deletion (Fig. 8). These results suggest that the regulation system of TH gene expression by DJ-1·PSF is present in human cells but not in mouse cells. Our study, therefore, shows one reason for no loss of dopamine in DJ-1-knock-out mice.Because DJ-1 has multiple functions to inhibit cell death (25Xu J. Zhong N. Wang H. Elias J.E. Kim C.Y. Woldman I. Pifl C. Gygi S.P. Geula C. Yankner B.A. Hum. Mol. Genet. 2005; 14: 1231-1241Crossref PubMed Scopus (220) Google Scholar, 26Canet-Avilés R.M. Wilson M.A. Miller D.W. Ahmad R. McLendon C. Bandyopadhyay S. Baptista M.J. Ringe D. Petsko G.A. Cookson M.R. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 9103-9108Crossref PubMed Scopus (894) Google Scholar, 27Taira T. Saito Y. Niki T. Iguchi-Ariga S.M. Takahashi K. Ariga H. EMBO Rep. 2004; 5: 213-218Crossref PubMed Scopus (734) Google Scholar, 29Martinat C. Shendelman S. Jonason A. Leete T. Beal M.F. Yang L. Floss T. Abeliovich A. PLoS Biol. 2004; 2: e327Crossref PubMed Scopus (242) Google Scholar, 39Yokota T. Sugawara K. Ito K. Takahashi R. Ariga H. Mizusawa H. Biochem. Biophys. Res. Commun. 2003; 312: 1342-1348Crossref PubMed Scopus (327) Google Scholar, 40Junn E. Taniguchi H. Jeong B.S. Zhao X. Ichijo H. Mouradian M.M. Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 9691-9696Crossref PubMed Scopus (284) Google Scholar) and the loss of DJ-1 functions causes early onset Parkinson disease (2Bonifati V. Rizzu P. van Baren M.J. Schaap O. Breedveld G.J. Krieger E. Dekker M.C. Squitieri F. Ibanez P. Joosse M. van Dongen J.W. Vanacore N. van Swieten J.C. Brice A. Meco G. van Duijn C.M. Oostra B.A. Heutink P. Science. 2003; 299: 256-259Crossref PubMed Scopus (2195) Google Scholar, 16Hedrich K. Djarmati A. Schäfer N. Hering R. Wellenbrock C. Weiss P.H. Hilker R. Vieregge P. Ozelius L.J. Heutink P. Bonifati V. Schwinger E. Lang A.E. Noth J. Bressman S.B. Pramstaller P.P. Riess O. Klein C. Neurology. 2004; 62: 389-394Crossref PubMed Scopus (176) Google Scholar), it is surprising that DJ-1-knock-out mice appear normal without histological abnormalities although exhibiting minor motor deficits (14Abou-Sleiman P.M. Healy D.G. Quinn N. Lees A.J. Wood N.W. Ann. Neurol. 2003; 54: 283-286Crossref PubMed Scopus (319) Google Scholar, 18Niki T. Takahashi-Niki K. Taira T. Iguchi-Ariga S.M. Ariga H. Mol. Cancer Res. 2003; 1: 247-261PubMed Google Scholar, 41Park J. Kim S.Y. Cha G.H. Lee S.B. Kim S. Chung J. Gene. 2005; 361: 133-139Crossref PubMed Scopus (182) Google Scholar). Although genetically engineered mice are valuable tools for understanding neurodegenerative diseases, they often do not reproduce all of the symptoms and pathological hallmarks of human diseases, probably due to the sum of multiple factors, including compensatory response, short life span, and difference in biological systems. Although we showed one possibility, that regulation of TH gene expression by DJ-1 differs in humans and mice, a better animal model of DJ-1 deficiency is needed to fully understand the function of DJ-1. It has very recently been reported that mice with double knock-out of DJ-1 and Ret, a receptor for glial cell line-derived neurotrophic factor, displayed trophically impaired dopaminergic neurons, suggesting that degeneration of dopaminergic neurons by DJ-1 requires an additional factor(s) (42Aron L. Klein P. Pham T.T. Kramer E.R. Wurst W. Klein R. PLoS Biol. 2010; 8: e1000349Crossref PubMed Scopus (48) Google Scholar).Several groups have established Drosophila models of DJ-1 deficiency (11Kitada T. Pisani A. Porter D.R. Yamaguchi H. Tscherter A. Martella G. Bonsi P. Zhang C. Pothos E.N. Shen J. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 11441-11446Crossref PubMed Scopus (403) Google Scholar, 38Chen L. Cagniard B. Mathews T. Jones S. Koh H.C. Ding Y. Carvey P.M. Ling Z. Kang U.J. Zhuang X. J. Biol. Chem. 2005; 280: 21418-21426Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar, 43Yang Y. Gehrke S. Haque M.E. Imai Y. Kosek J. Yang L. Beal M.F. Nishimura I. Wakamatsu K. Ito S. Takahashi R. Lu B. Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 13670-13675Crossref PubMed Scopus (301) Google Scholar). Different strategies to inactivate DJ-1 have, however, led to distinct phenotypes (41Park J. Kim S.Y. Cha G.H. Lee S.B. Kim S. Chung J. Gene. 2005; 361: 133-139Crossref PubMed Scopus (182) Google Scholar). Interestingly, only a study using siRNA to inactivate the Drosophila DJ-1 gene demonstrated an age-dependent decrease in the number of TH-positive neurons and total brain dopamine content that resembles the neuropathology in PD patients (43Yang Y. Gehrke S. Haque M.E. Imai Y. Kosek J. Yang L. Beal M.F. Nishimura I. Wakamatsu K. Ito S. Takahashi R. Lu B. Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 13670-13675Crossref PubMed Scopus (301) Google Scholar). Although DJ-1 siRNA-induced apoptosis certainly contributes to this observation, it would be of interest to examine whether DJ-1 inactivation leads to transcriptional down-regulation of TH gene expression in Drosophila as well. IntroductionParkinson disease (PD) 3The abbreviations used are: PDParkinson diseaseTHtyrosine hydroxylasehTHhuman THmTHmouse THl-DOPA4-dihydroxy-l-phenylalaninePSFpolypyrimidine tract-binding protein-associated splicing factor. is the most common movement disorder caused by gradual loss of dopaminergic neurons in the substantia nigra pars compacta. Although most cases are sporadic, 5–10% of PD patients carry mutations with a Mendelian inheritance, and mutations in parkin, DJ-1, and PINK1 genes have been linked to autosomal recessive forms of PD (1Kitada T. Asakawa S. Hattori N. Matsumine H. Yamamura Y. Minoshima S. Yokochi M. Mizuno Y. Shimizu N. Nature. 1998; 392: 605-608Crossref PubMed Scopus (4123) Google Scholar, 2Bonifati V. Rizzu P. van Baren M.J. Schaap O. Breedveld G.J. Krieger E. Dekker M.C. Squitieri F. Ibanez P. Joosse M. van Dongen J.W. Vanacore N. van Swieten J.C. Brice A. Meco G. van Duijn C.M. Oostra B.A. Heutink P. Science. 2003; 299: 256-259Crossref PubMed Scopus (2195) Google Scholar, 3Valente E.M. Abou-Sleiman P.M. Caputo V. Muqit M.M. Harvey K. Gispert S. Ali Z. Del Turco D. Bentivoglio A.R. Healy D.G. Albanese A. Nussbaum R. González-Maldonado R. Deller T. Salvi S. Cortelli P. Gilks W.P. Latchman D.S. Harvey R.J. Dallapiccola B. Auburger G. Wood N.W. Science. 2004; 304: 1158-1160Crossref PubMed Scopus (2630) Google Scholar). Although a large number of studies have been carried out to determine whether inactivation of each of these genes in mice or fruit flies results in progressive and selective loss of dopaminergic neurons, almost all of the studies, including studies using mice with single or triple deficiency in parkin, DJ-1, and PINK1 genes, showed no loss of dopaminergic neurons in the substantia nigra pars compacta (4Goldberg M.S. Fleming S.M. Palacino J.J. Cepeda C. Lam H.A. Bhatnagar A. Meloni E.G. Wu N. Ackerson L.C. Klapstein G.J. Gajendiran M. Roth B.L. Chesselet M.F. Maidment N.T. Levine M.S. Shen J. J. Biol. Chem. 2003; 278: 43628-43635Abstract Full Text Full Text PDF PubMed Scopus (714) Google Scholar, 5Goldberg M.S. Pisani A. Haburcak M. Vortherms T.A. Kitada T. Costa C. Tong Y. Martella G. Tscherter A. Martins A. Bernardi G. Roth B.L. Pothos E.N. Calabresi P. Shen J. Neuron. 2005; 45: 489-496Abstract Full Text Full Text PDF PubMed Scopus (435) Google Scholar, 6Itier J.M. Ibanez P. Mena M.A. Abbas N. Cohen-Salmon C. Bohme G.A. Laville M. Pratt J. Corti O. Pradier L. Ret G. Joubert C. Periquet M. Araujo F. Negroni J. Casarejos M.J. Canals S. Solano R. Serrano A. Gallego E. Sanchez M. Denefle P. Benavides J. Tremp G. Rooney T.A. Brice A. Garcia de Yebenes J. Hum. Mol. Genet. 2003; 12: 2277-2291Crossref PubMed Scopus (439) Google Scholar, 7Pesah Y. Pham T. Burgess H. Middlebrooks B. Verstreken P. Zhou Y. Harding M. Bellen H. Mardon G. Development. 2004; 131: 2183-2194Crossref PubMed Scopus (366) Google Scholar, 8Perez F.A. Palmiter R.D. Proc. Natl. Acad. Sci. U.S.A. 2005; 102: 2174-2179Crossref PubMed Scopus (357) Google Scholar, 9Andres-Mateos E. Perier C. Zhang L. Blanchard-Fillion B. Greco T.M. Thomas B. Ko H.S. Sasaki M. Ischiropoulos H. Przedborski S. Dawson T.M. Dawson V.L. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 14807-14812Crossref PubMed Scopus (385) Google Scholar, 10Görner K. Holtorf E. Waak J. Pham T.T. Vogt-Weisenhorn D.M. Wurst W. Haass C. Kahle P.J. J. Biol. Chem. 2007; 282: 13680-13691Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 11Kitada T. Pisani A. Porter D.R. Yamaguchi H. Tscherter A. Martella G. Bonsi P. Zhang C. Pothos E.N. Shen J. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 11441-11446Crossref PubMed Scopus (403) Google Scholar, 12Wood-Kaczmar A. Gandhi S. Yao Z. Abramov A.Y. Miljan E.A. Keen G. Stanyer L. Hargreaves I. Klupsch K. Deas E. Downward J. Mansfield L. Jat P. Taylor J. Heales S. Duchen M.R. Latchman D. Tabrizi S.J. Wood N.W. PLoS ONE. 2008; 3: e2455Crossref PubMed Scopus (262) Google Scholar).DJ-1 was first identified by our group as a novel oncogene that transformed mouse NIH3T3 cells in cooperation with activated H-ras (13Nagakubo D. Taira T. Kitaura H. Ikeda M. Tamai K. Iguchi-Ariga S.M. Ariga H. Biochem. Biophys. Res. Commun. 1997; 231: 509-513Crossref PubMed Scopus (660) Google Scholar). Deletion and point (L166P) mutations of DJ-1 have been shown to be responsible for the onset of familial Parkinson disease, PARK7 (2Bonifati V. Rizzu P. van Baren M.J. Schaap O. Breedveld G.J. Krieger E. Dekker M.C. Squitieri F. Ibanez P. Joosse M. van Dongen J.W. Vanacore N. van Swieten J.C. Brice A. Meco G. van Duijn C.M. Oostra B.A. Heutink P. Science. 2003; 299: 256-259Crossref PubMed Scopus (2195) Google Scholar), and other homozygous and heterozygous mutations of DJ-1 have been identified in patients with familial or sporadic PD (14Abou-Sleiman P.M. Healy D.G. Quinn N. Lees A.J. Wood N.W. Ann. Neurol. 2003;" @default.
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W2005917373 cites W1985399632 @default.
W2005917373 cites W1990847293 @default.
W2005917373 cites W1992621490 @default.
W2005917373 cites W2005764967 @default.
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W2005917373 cites W2012112859 @default.
W2005917373 cites W2026841498 @default.
W2005917373 cites W2031898930 @default.
W2005917373 cites W2039126848 @default.
W2005917373 cites W2047916240 @default.
W2005917373 cites W2054066978 @default.
W2005917373 cites W2058074045 @default.
W2005917373 cites W2059209321 @default.
W2005917373 cites W2064318682 @default.
W2005917373 cites W2065060908 @default.
W2005917373 cites W2070766926 @default.
W2005917373 cites W2074397899 @default.
W2005917373 cites W2076196975 @default.
W2005917373 cites W2077822590 @default.
W2005917373 cites W2088962120 @default.
W2005917373 cites W2091026319 @default.
W2005917373 cites W2096991937 @default.
W2005917373 cites W2104382960 @default.
W2005917373 cites W2107977469 @default.
W2005917373 cites W2129698492 @default.
W2005917373 cites W2131988270 @default.
W2005917373 cites W2136347558 @default.
W2005917373 cites W2136388422 @default.
W2005917373 cites W2145664571 @default.
W2005917373 cites W2151430711 @default.
W2005917373 cites W2158259597 @default.
W2005917373 cites W2160681852 @default.
W2005917373 cites W2161188071 @default.
W2005917373 cites W2170748127 @default.
W2005917373 cites W2171873547 @default.
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