Regulatory mechanism of PML body function by MORC3

• Project/Area Number: 21590326
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• Principal Investigator: INOUE Norimitsu 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 部長 (80252708)
• Co-Investigator(Renkei-kenkyūsha): AKAZAWA Takashi 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 研究員 (80359299)
• Research Collaborator: TAKAHASHI Keiko Lawrence Berkeley National Laboratory, Postdoctoral fellow ; MIMURA Yasuhiro 奈良先端科学技術大学院大学, 理化学研究所, 特別研究員
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); 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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: MORC3 / PMLボディ / SUMO / 白血病 / 核ダイナミクス / 癌

Research Abstract

The PML-RARα fusion proteins cause acute promyelocytic leukemia(APL). The PML proteins form nuclear foci called PML-body in normal cells. However, PML-nuclear body is disrupted in APL cells. We focus on the localization mechanisms of MORC3 as a drug target of APL because the localization of MORC3 on PML-nuclear body is also disrupted in APL cells. In this study, we show that MORC3 colocalizes with PML by a two-step molecular mechanism.

Research Products

• [Journal Article] Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors (2012)
  • Author(s): H.Shime
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 6 Pages: 2066-2071
  • DOI: 10.1073/pnas.1113099109
  • Peer Reviewed
• [Journal Article] Deregulated expression of HMGA2 is implicated in clonal expansion of PIGA deficient cells in paroxysmal nocturnal haemoglobinuria (2012)
  • Author(s): Murakami, Y., N. Inoue, T. Shichishima, R. Ohta, H. Noji, Y. Maeda, J. Nishimura, Y. Kanakura and T. Kinoshita
  • Journal Title: Br. J. Haematol Volume: 156 Issue: 3 Pages: 383-387
  • DOI: 10.1111/j.1365-2141.2011.08914.x
  • Peer Reviewed
• [Journal Article] IL17A(interleukin 17A) (2011)
  • Author(s): Inoue, N. and Akazawa, T
  • Journal Title: Atlas of Genetics and Cytogenetics in Oncology and Haematology Volume: 15(8) Issue: 8 Pages: 662-666
  • DOI: 10.4267/2042/46016
• [Journal Article] Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through dendritic cell TLR2 (2011)
  • Author(s): Sawahata, R., Shime, H., Yamazaki, S., Inoue, N., Akazawa, T., Fujimoto, Y., Fukase, K., Matsumoto, M. and Seya, T.
  • Journal Title: Microbes and Infection Volume: 13 Issue: 4 Pages: 350-358
  • DOI: 10.1016/j.micinf.2010.12.003
  • NAID: 120002912001
  • Peer Reviewed
• [Journal Article] IL-23 dependent and-independent enhancement pathway of IL-17A production by lactic acid (2011)
  • Author(s): Yabu, M., Shime, H., Hara, H., Saito, T., Matsumoto, M., Seya, T., Akazawa, T. and Inoue, N.
  • Journal Title: Intl Immunology Volume: 23(1) Issue: 1 Pages: 29-41
  • DOI: 10.1093/intimm/dxq455
  • Peer Reviewed
• [Journal Article] IL23A(interleukin 23, alpha subunit p19) (2011)
  • Author(s): Inoue, N
  • Journal Title: Atlas of Genetics and Cytogenetics in Oncology and Haematology Volume: 15(2) Issue: 2 Pages: 191-194
  • DOI: 10.4267/2042/44965
• [Journal Article] IL-23 dependent and -independent enhancement pathway of I L-17A production by lactic acid. (2011)
  • Author(s): Yabu, M.
  • Journal Title: International Immunology Volume: 23 Pages: 29-41
  • Peer Reviewed
• [Journal Article] IL17A (interleukin 17A) (2011)
  • Author(s): Inoue, N.
  • Journal Title: Atlas of Genetics and Cytogenetics in Oncology and Haematology
• [Journal Article] INFγmarkedly cooperates with intratumoral dendritic cell vaccine in dog tumor models (2010)
  • Author(s): Mito K, Sugiura K, Ueda K, Hori T, Akazawa T, Yamate J, Hatoya S, Inaba M, Inoue N, Ikehara S, Inaba T
  • Journal Title: Cancer Res Volume: 70巻 Issue: 18 Pages: 7093-7101
  • DOI: 10.1158/0008-5472.can-10-0600
  • Peer Reviewed
• [Journal Article] Adjuvant engineering for cancer immunotherapy : Development of a synthetic TLR2 ligand with increased cell adhesion (2010)
  • Author(s): Akazawa, T., Inoue, N., Shime, H., Kodama, K., Matsumoto, M. and Seya, T.
  • Journal Title: Cancer Science Volume: 101(7) Issue: 7 Pages: 1596-1603
  • DOI: 10.1111/j.1349-7006.2010.01583.x
  • NAID: 10026594411
  • Peer Reviewed
• [Journal Article] Effect of IL-12 on the canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4 (2010)
  • Author(s): Sugiura K, Wijewardana V, Fujimoto M, Akazawa T, Yahata M, Mito K, Hatoya S, Inoue N, Inaba T
  • Journal Title: Vet. Immunol. Immunopathol Volume: 137巻 Issue: 3-4 Pages: 322-326
  • DOI: 10.1016/j.vetimm.2010.06.006
  • Peer Reviewed
• [Journal Article] Two-step colocalization of MORC3 with PML nuclear bodies (2010)
  • Author(s): Mimura, Y., Takahashi, K., Kawata, K., Akazawa, T. and Inoue, N
  • Journal Title: J. Cell Science Volume: 123(12) Issue: 12 Pages: 2014-2024
  • DOI: 10.1242/jcs.063586
  • Peer Reviewed
• [Journal Article] Two-step colocalization of MORC3 with PML nuclear bodies. (2010)
  • Author(s): Mimura, Y.
  • Journal Title: J.Cell Science Volume: 123 Pages: 2014-2024
  • Peer Reviewed
• [Journal Article] Adjuvant engineering for cancer immunotherapy : Development of a synthetic TLR2 ligand with increased cell adhesion. (2010)
  • Author(s): Akazawa, T.
  • Journal Title: Cancer Science Volume: 101 Pages: 1596-1603
  • NAID: 10026594411
  • Peer Reviewed
• [Journal Article] Effect of IL-12 on the canine dendritic cell maturation following differentiation induced by granulocyte-macrophage CSF and IL-4. (2010)
  • Author(s): Sugiura, K.
  • Journal Title: Veterinary immunology & immunopathology Volume: 137 Pages: 322-326
  • Peer Reviewed
• [Journal Article] Interferon-gamma markedly cooperates with intratumoral DC vaccine in dog tumor models. (2010)
  • Author(s): Mito, K.
  • Journal Title: Cancer Research Volume: 70 Pages: 7093-7101
  • Peer Reviewed
• [Journal Article] IL23A (interleukin 23, alpha subunit p19) (2010)
  • Author(s): Inoue, N.
  • Journal Title: Atlas of Genetics and Cytogenetics in Oncology and Haematology
  • Peer Reviewed
• [Journal Article] Two-step colocalization of MORC3 with PML nuclear bodies. (2010)
  • Author(s): Mimura, Y.
  • Journal Title: J.Cell Science (印刷中)
  • Peer Reviewed
• [Journal Article] Adjuvant engineering for cancer immunotherapy : Development of a synthetic TLR2 ligand with increased cell adhesion. (2010)
  • Author(s): Akazawa, T.
  • Journal Title: Cancer Science (印刷中)
  • NAID: 10026594411
  • Peer Reviewed
• [Journal Article] TLR刺激によるTh17細胞の増加 (2009)
  • Author(s): 志馬寛明、井上徳光、松本美佐子、瀬谷司
  • Journal Title: 臨床免疫・アレルギー科 Volume: 51(5) Pages: 79-486
• [Presentation] 乳酸は、がん微小環境の炎症メディエーターとして働く (2011)
  • Author(s): 井上徳光
  • Organizer: 平成23年度遺伝病制御研究所共同研究集会
  • Place of Presentation: 札幌(招待講演)
  • Year and Date: 2011-09-06
• [Presentation] 乳酸は、がん微小環境の炎症メディエーターとして働く (2011)
  • Author(s): 井上徳光
  • Organizer: 第48回補体シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2011-09-02
• [Presentation] 腫瘍における乳酸産生の制御は、抗腫瘍免疫応答を増強する (2011)
  • Author(s): 大橋敏充・赤澤隆・井上徳光
  • Organizer: 第70回日本癌学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 乳酸は、がん微小環境の炎症メディエーターとして働く (2011)
  • Author(s): 井上徳光
  • Organizer: 平成23年度遺伝病制御研究所共同研究集会
  • Place of Presentation: 札幌
• [Presentation] 抗がん免疫療法のターゲットとしての乳酸シグナル経路の可能性 (2011)
  • Author(s): 井上徳光
  • Organizer: 第48回補体シンポジウム
  • Place of Presentation: 名古屋
• [Presentation] Mechanisms of increased IL-17A production by lactic acid (2010)
  • Author(s): Inoue, N.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-25
• [Presentation] Two-step colocalization mechanism of MORC3 with PML-nuclear body (2010)
  • Author(s): Inoue, N.
  • Organizer: The LXXV Cold Spring Harbor Symposium Nuclear Organization & Function
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2010-06-04
• [Presentation] Expression of HMGA2 in blood cells from patients with paroxysmal nocturnal hemoglobinuria (2010)
  • Author(s): Murakami Y, Inoue N, Shichishima T, Noji H, Nishimura J, Kanakura Y, Kinoshita T
  • Organizer: 52nd ASH annual meeting
  • Place of Presentation: Orland, USA
• [Presentation] 乳酸によるIL-23非依存的なIL-17産生増強経路 (2010)
  • Author(s): 井上徳光、藪政彦、志馬寛明、松本美佐子、瀬谷司、赤澤隆
  • Organizer: 第47回補体シンポジウム
  • Place of Presentation: 福島
• [Presentation] Mechanisms of increased IL-17A production by lactic acid (2010)
  • Author(s): Inoue N, Yabu M, Akazawa T, Matsumoto M, Seya T, Shime H
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸
• [Presentation] Two-step colocalization mechanism of MORC3 with PML-nuclear body LXXV Cold Spring Harbor (2010)
  • Author(s): Inoue N, Mimura Y, Takahashi K, Akazawa T
  • Organizer: Symposium-Nucelar organization & function
  • Place of Presentation: New York, USA
• [Presentation] MORC3は、2ステップでPMLボディと共局在する (2010)
  • Author(s): 三村恭弘、高橋桂子、河田規予、赤澤隆、井上徳光
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
• [Presentation] Novel molecular mechnism of nuclear domain formation via ATP-cycle and SUMOylation (2009)
  • Author(s): 三村恭弘
  • Organizer: 第32回分子生物学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-12
• [Presentation] Promyelocytic leukemia(PML)蛋白と相互作用するMORC3ATPaseによる造血分化制御 (2009)
  • Author(s): 井上徳光
  • Organizer: 第15回血液科学セミナー
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2009-11-22
• [Presentation] PMLボディに局在するMorc3ノックアウトマウスの造血分化異常 (2009)
  • Author(s): 井上徳光
  • Organizer: 第71回日本血液学学術集会
  • Place of Presentation: 京都国際会館(京都府)
  • Year and Date: 2009-10-24
• [Presentation] MORC3の核内ドメイン形成とPML-NBとの会合メカニズム (2009)
  • Author(s): 三村恭弘
  • Organizer: 核ダイナミクス研究会
  • Place of Presentation: ラフォーレ修善寺(静岡県)
  • Year and Date: 2009-06-19
• [Presentation] 乳酸はTh1/Th17バランスをTh17細胞側に傾ける (2009)
  • Author(s): 藪政彦、志馬寛明、赤澤隆、井上徳光
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] Lactic acid is a new inflammatory mediator secreted from tumor (2009)
  • Author(s): 井上徳光
  • Organizer: 第32回分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Novel molecular mechanism of nuclear domain formation via ATP-cycle and SUMOylation (2009)
  • Author(s): 三村恭弘、赤澤隆、井上徳光
  • Organizer: 第32回分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] PMLボディに局在するMorc3ノックアウトマウスの造血分化異 (2009)
  • Author(s): 井上徳光
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Promyelocytic leukemia(PML)蛋白と相互作用するMORC3ATPaseによる造血分化異常 (2009)
  • Author(s): 井上徳光
  • Organizer: 第15回血液学セミナー
  • Place of Presentation: 東京
• [Presentation] MORC3の核内ドメイン形成とPML-NBとの会合メカニズム (2009)
  • Author(s): 三村恭弘、赤澤隆、高橋桂子、井上徳光
  • Organizer: 第8回核ダナミクス研究会
  • Place of Presentation: 伊豆
• [Presentation] 乳酸はトル様受容体リガンドを用いた抗癌免疫療法の効果を増強する (2009)
  • Author(s): 井上徳光
  • Organizer: 第13回がん免疫学会総会
  • Place of Presentation: 北九州
• [Book] 補体と獲得免疫 (2011)
  • Author(s): 井上徳光
  • Publisher: 補体への招待・メディカルビュー社
• [Remarks]
  • URL: http://www.mc.pref.osaka.jp/omc2/genetics.html
• [Remarks]
  • URL: http://www.mc.pref.osaka.jp/omc2/genetics.html
• [Remarks]
  • URL: http://www.mc.pref.osaka.jp/omc2/genetics.html
• [Patent(Industrial Property Rights)] 新規人工設計リポペプチド (2012)
  • Inventor(s): 赤澤隆・井上徳光
  • Industrial Property Rights Holder: 大阪府立病院機構
  • Industrial Property Number: 2012-076273
  • Filing Date: 2012-03-29
• [Patent(Industrial Property Rights)] 新規人工設計リポペプチド (2012)
  • Inventor(s): 赤澤隆, 井上徳光
  • Industrial Property Rights Holder: 大阪府立病院機構
  • Industrial Property Number: 2012-076273
  • Filing Date: 2012-03-29