Study on transcriptional activation mechanism of DJ-1 gene(PARK7) and the trial to Parkinson's disease cure development

• Project/Area Number: 21590091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Yamanashi
• Principal Investigator: TAIRA Takahiro 山梨大学, 大学院・医学工学総合研究部, 教授 (70197036)
• Co-Investigator(Kenkyū-buntansha): OHGA Rie 山梨大学, 医学部, 助手 (00160432) ; FUJIMURO Masahiro 山梨大学, 大学院・医学工学総合研究部, 准教授 (20360927)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: DJ-1 / パーキンソン病 / 酸化ストレス / 神経変性疾患 / 転写調節 / 神経細胞 / 神経膠細胞 / 細胞死 / アストロサイト / 癌遺伝子

Research Abstract

The DJ-1 protein which is a familial Parkinson's disease(PARK7) causative gene product. It was already shown clearly that DJ-1 protein is associated with tyrosine hydroxylase(TH). Although it had been unknown the mechanism of transcriptional activation of TH gene by DJ-1 protein. In this research, We clarified trans-activation mechanism TH gene by DJ-1 protein. Also among human, mouse and rat, it was shown clearly that a mechanism has a difference.

Research Products

• [Journal Article] The Ubiquitin System and Kaposi's Sarcoma-Associated Herpesvirus (2012)
  • Author(s): Ashizawa A, Higashi C, Masuda K, Ohga R, Taira T, Fujimuro M.
  • Journal Title: Front. Microbiol Volume: 3 Pages: 1-10
  • Peer Reviewed
• [Journal Article] The ubiquitin sysytem and Kaposi's sarcoma-associated herpesvirus (2012)
  • Author(s): Ashizawa A, 他5名
  • Journal Title: Frontiers in Microbiology Volume: 3 Pages: 1-10
  • DOI: 10.3389/fmicb.2012.00066
  • Peer Reviewed
• [Journal Article] The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues : implication for pathogenesis of Rett syndrome (2011)
  • Author(s): Miyake K, Hirasawa T, Soutome M, Itoh M, Goto Y, Endoh K, Takahashi K, Kudo S, Nakagawa T, Yokoi S, Taira T, Inazawa J, Kubota T.
  • Journal Title: BMC Neurosci Volume: 8 ; 12 Pages: 81-81
  • Peer Reviewed
• [Journal Article] Protection against dopaminergic neurodegeneration in Parkinson's disease-model animals by amodulator of the oxidized form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7 (2011)
  • Author(s): Inden M, Kitamura Y, Takahashi K, Takata K, Ito N, Niwa R, Funayama R, Nishimura K, Taniguchi T, Honda T, Taira T, Ariga H.
  • Journal Title: J Pharmacol Sci Volume: 117(3) Pages: 189-203
  • Peer Reviewed
• [Journal Article] Protection Against Dopaminergic Neurodegeneration in Parkinson's Disease-Model Animals by a Modulator of the Oxidized Form of DJ-1, a Wild-type of Familial Parkinson's Disease-Linked PARK7 (2011)
  • Author(s): Inden, M., Kitamura, M., Takahashi, K., Takata, K., Ito, N., Niwa, R., Funayama, R., Nishimura, K., Taniguchi, T., Honda, T., Taira, T., Ariga, H.
  • Journal Title: Journal of Pharmacological Sciences Volume: 117 Issue: 3 Pages: 189-203
  • DOI: 10.1254/jphs.11151FP
  • NAID: 10030453398
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Journal Article] S. M. M.(2010) Human DJ-1-specific transcriptional activation of tyrosine hydroxylase gene (2010)
  • Author(s): Ishikawa, S., Taira, T., Takahashi-Niki, K., Niki, T., Ariga, H. and Iguchi-Ariga
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 39718-39721
  • Peer Reviewed
• [Journal Article] HumanDJ-1-specific transcriptional activation of tyrosine hydroxylase gene. (2010)
  • Author(s): Ishikawa, S
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 39718-39731
  • Peer Reviewed
• [Journal Article] Oxidative neurodegeneration is prevented by UCP0045037, an allosteric modulator for the reduced form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7 (2009)
  • Author(s): Yamane, K., Kitamura, Y., Yanagida, T., Takata, T., Yanagisawa, D., Taniguchi, T., Taira, T. and Ariga, H.
  • Journal Title: Int. J. Mol. Sci Volume: 10(11) Pages: 4789-4804
  • NAID: 120001720441
  • Peer Reviewed
• [Journal Article] S. M. M.(2009) DJ-1 binds to mitochondrial complex I and maintains its activity. (2009)
  • Author(s): Hayashi, T., Ishimori, C., Takahashi-Niki, K., Taira, T., Kim, Y-C., Maita, H., Maita, C., Ariga, H. and Iguchi-Ariga
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 390 Pages: 667-672
  • Peer Reviewed
• [Journal Article] S. M. M.(2009) Oxidative status of DJ-1-dependent activation of dopamine synthesis through interaction of tyrosine hydroxylase and4-dihydroxy-1-phenylalanine(1-DOPA) decarboxylase with DJ-1 (2009)
  • Author(s): Ishikawa, S., Taira, T., Niki, T., Takahashi-Niki, K., Maita, C., Maita, H., Ariga, H. and Iguchi-Ariga
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 28832-28844
  • Peer Reviewed
• [Journal Article] Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN (2009)
  • Author(s): Kim, Y.-C., Kitaura, H., Taira, T., Iguchi-Ariga, S. M. M. and Ariga, H.
  • Journal Title: Int. J. Oncol Volume: 35 Pages: 1331-1341
  • NAID: 120002646831
  • Peer Reviewed
• [Journal Article] Neuroprotective effect of the antiparkinsonian drug pramipexole against nigrostriatal dopaminergic degeneration in rotenone-treated mice (2009)
  • Author(s): Inden, M., Kitamura, Y., Tamaki, A., Yanagida, T., Shibaike, T., Yamamoto, A., Takata, K., Yasui, H., Taira, T., Ariga, H. and Taniguchi, T.
  • Journal Title: Neurochem. Int Volume: 55(8) Pages: 760-767
  • Peer Reviewed
• [Journal Article] Protection against oxida tive stress-induced neurodegeneration by amodulator for DJ-1, a wild-type of familial Parkinson's disease-linked PARK7 (2009)
  • Author(s): Yanagida, T., Kitamura, Y., Yamane, K., Takahashi, K., Takata, K., Yanagisawa, D., Yasui, H., Taniguchi, T., Taira, T., Honda, T. and Ariga, H.
  • Journal Title: J. Pharmacol. Sci Volume: 109 Pages: 463-468
  • Peer Reviewed
• [Journal Article] Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury (2009)
  • Author(s): Yanagida, 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. and Ariga, H.
  • Journal Title: Oxidative Medicine & Cellular Longevity Volume: 1 Pages: 36-42
  • NAID: 120005350101
  • Peer Reviewed
• [Journal Article] Protection against oxidative stress-induced neurodegeneration by a modulator for DJ-1, a wild-type of familial Parkinson's disease-linked PARK7 (2009)
  • Author(s): Yanagida, T.
  • Journal Title: JOURNAL OF PHARMACOLOGICAL SCIENCES 109 Pages: 463-468
  • Peer Reviewed
• [Journal Article] Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury. (2009)
  • Author(s): Yanagida, T.
  • Journal Title: Oxidative Medicine & Cellular Longevity 1 Pages: 36-42
  • Peer Reviewed
• [Journal Article] Neuroprotective effect of the antiparkinsonian drug pramipexole against nigrostriatal dopaminergic degeneration in rotenone-treated mice. (2009)
  • Author(s): Inden, M.
  • Journal Title: NEUROCHEMISTRY INTERNATIONAL 55 Pages: 760-767
  • Peer Reviewed
• [Journal Article] Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN. (2009)
  • Author(s): Kim, Y.-C.,
  • Journal Title: INTERNATIONAL JOURNAL OF ONCOLOGY 35 Pages: 1331-1341
  • Peer Reviewed
• [Journal Article] Oxidative status of DJ-1-dependent activation of dopamine synthesis through interaction of tyrosine hydroxylase and 4-dihydroxy-1-phenylalanine(1-DOPA)decarboxylase with DJ-1 (2009)
  • Author(s): Ishikawa, S.
  • Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY 284 Pages: 28832-28844
  • Peer Reviewed
• [Journal Article] DJ-1 binds to mitochondrial complex I and maintains its activity. (2009)
  • Author(s): Hayashi, T.
  • Journal Title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 390 Pages: 667-672
  • Peer Reviewed
• [Journal Article] Oxidative neurodegeneration is prevented by UCP0045037, an allosteric modulator for the reduced form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7. (2009)
  • Author(s): Yamane, K.
  • Journal Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 10 Pages: 4789-4804
  • Peer Reviewed
• [Presentation] 家族性パーキンソン病(PARK7)原因遺伝子産物DJ-1タンパク質の生物種差 (2011)
  • Author(s): 平敬宏
  • Organizer: 第13回応用薬理シンポジウム
  • Place of Presentation: 船橋市
  • Year and Date: 2011-09-03
• [Presentation] 家族性パーキンソン病(PARK7)原因遺伝子産物DJ-1タンパク質の生物種差 (2011)
  • Author(s): 平敬宏
  • Organizer: 第13回応用薬理シンポジウム
  • Place of Presentation: 船橋市民創造館きららホール(千葉県船橋市)(招待講演)
  • Year and Date: 2011-09-03
• [Presentation] がんウイルスによるアポトーシス制御因子p32/HABP1/gC1qRの機能阻害 (2010)
  • Author(s): 鈴木千恵,手石方康弘,笹島仁,横澤英吉,平敬宏,藤室雅弘
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-12
• [Presentation] がんウイルスによるアポトーシス制御因子p32/HABP1/gC1qRの機能阻害 (2010)
  • Author(s): 鈴木千恵
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同会
  • Place of Presentation: 兵庫県神戸市神戸ポートアイランド
  • Year and Date: 2010-12-10
• [Presentation] Identification of MeCP2-targetsynaptic molecules associated with pathogenesis of Rett syndrome (2010)
  • Author(s): Kunio Miyake, Takae Hirasawa, Masaki soutome, Masayuki, Itoh, Yu-ichi Goto, Kazushi Endoh, Shinichi Kudou, Sana Yokoi, Takahiro Taira, Johji Inazawa, Takeo Kubota
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-08
• [Presentation] Identification of MeCP2-target synaptic molecules associated with patho genesis of Rett syndrome (2010)
  • Author(s): 三宅邦夫
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同会
  • Place of Presentation: 兵庫県神戸市神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] ヒトDJ-1特異的なチロシン水酸化酵素遺伝子の転写活性化調節 (2010)
  • Author(s): 石川静麻
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会
  • Place of Presentation: 神戸国際会議場、神戸国際展示場(神戸)
  • Year and Date: 2010-09-13
• [Presentation] ヒトDJ-1特異的なチロシン水酸化酵素遺伝子の転写活性化調節 (2010)
  • Author(s): 石川静麻,平敬宏,仁木加寿子,仁木剛史,有賀寛芳,有賀早苗
  • Organizer: 第33回日本神経科学大会・第53回日本神経化学会大会第20回日本神経回路学会大会合同大会
  • Place of Presentation: 神戸市
  • Year and Date: 2010-09-03
• [Presentation] 家族性パーキンソン病(PARK7)原因遺伝子産物DJ-1タンパク質の機能と今後の研究課題 (2010)
  • Author(s): 平敬宏
  • Organizer: 第17回順天堂大学神経学セミナー
  • Place of Presentation: 東京都文京区
  • Year and Date: 2010-03-30
• [Presentation] Human DJ-1-dependent activation of dopamine biosynthesis through interction of tyrosine hydroxylase with DJ-1 (2009)
  • Author(s): 石川静麻,平敬宏,有賀寛芳,有賀早苗
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-12-09
• [Presentation] Human DJ-1-dependent activation of dopamine biosynthesis through interction of tyrosine hydroxylase with DJ-1 (2009)
  • Author(s): 石川静麻
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜 パシフィコ横浜
  • Year and Date: 2009-12-09
• [Presentation] Inhibition of PTEN phosphatase activity by the direct interaction of DJ-1 with PTEN under the oxidative conditions (2009)
  • Author(s): 金允哲,北浦廣剛,平敬宏,有賀早苗,有賀寛芳
  • Organizer: 第32回日本神経科学会大会
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-09-16
• [Presentation] Inhibition of PTEN phosphatase activity by the direct interaction of DJ-1 with PTEN under the oxidative conditions (2009)
  • Author(s): 金允哲
  • Organizer: 第32回日本神経科学会大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-09-16
• [Remarks]
  • URL: http://www.yamanashi.ac.jp/education/medical/basic/molbio/indexMCB.html
• [Remarks]
  • URL: http://www.med.yamanashi.ac.jp/basic/molbio/indexMCB.html
• [Remarks]
  • URL: http://www.med.yamanashi.ac.jp/basic/molbio/indexMCB.html