Analysis of the molecular function of Geminin in leukemogenesis

• Project/Area Number: 24790976
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: OHNO Yoshinori 広島大学, 原爆放射線医科学研究所, 助教 (10548986)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 白血病幹細胞 / Geminin / Hoxa9 / Mll-Af9 / 造血幹細胞 / E2F / Hox / MLL-AF9 / ユビキチン

Research Abstract

We demonstrated that Hoxa9 regulate the activity of hematopoietic stem cells (HSCs) through the ubiquitin-proteasom-mediated direct regulation of Geminin, indicating that Geminin acts as a central factor for regulating cellular proliferation and differentiation in HSCs. Recently, we have shown that Geminin egulates the transcriptional activity of E2F, a regulator of cell cycle, through the chromatin remodeling. These findings suggest that Geminin plays an important role in hematopoiesis and leukemogenesis

Research Products

• [Journal Article] Transcription of the Geminin gene is regulated loop (2014)
  • Author(s): Ohno Y, Saeki K, Yasunaga S, Kurogi T, Suzuki-Takedachi K, Shirai M, Mihara K, Yoshida K, Voncken JW, Ohtsubo M, Takihara Y
  • Journal Title: Mol Biol Cell Volume: 25(8) Pages: 1374-83
  • Peer Reviewed
• [Journal Article] Transcription of the Geminin gene is regulated by a negative-feedback loop. (2014)
  • Author(s): Ohno, Y., Saeki, K., Yasunaga, S., Kurogi. T., Suzuki-Takedachi, K., Shirai, M., Mihara K., Yoshida, K., Voncken J. W, Ohtsubo, M. & Takihara Y.
  • Journal Title: Mol. Biol. Cel Volume: 25(8) Issue: 8 Pages: 1374-1383
  • DOI: 10.1091/mbc.e13-09-0534
  • Peer Reviewed / Open Access
• [Journal Article] Hoxa9 transduction induces hematopoietic stem and progenitor cell activity through direct down-regulation of geminin protein (2013)
  • Author(s): Ohno Y, Yasunaga S, Janmohamed S, Ohtsubo M, Saeki K, Kurogi T, Mihara K, Iscove NN, Takihara Y
  • Journal Title: PLoS One Volume: 8(1)
  • Peer Reviewed
• [Journal Article] Scmh1 has E3 ubiquitin ligase activity for geminin and histone H2A and regulates geminin stability directly or indirectly via transcriptional repression of Hoxa9 and Hoxb4 (2013)
  • Author(s): Yasunaga S, Ohtsubo M, K, Kurogi T, Tanaka Ishizaki H, Shi HW, Miyoshi J, Takihara Y
  • Journal Title: Mol Cell Biol Volume: 33(4) Pages: 644-60
  • Peer Reviewed
• [Journal Article] Scmh1 has E3 ubiquitin ligase activity for Geminin and histone H2A and regulates Geminin stability directly or indirectly via transcription repression of Hoxa9 and Hoxb4 (2013)
  • Author(s): Yasunaga, S., Ohtsubo, M., Ohno, Y., Saeki, K., Kurogi. T., Tanaka-Okamoto, M., Ishizaki, H., Shirai, M., Mihara, K., Brock, H. W., Miyoshi, J. & Takihara Y
  • Journal Title: Mol. Cell. Biol. Volume: 33(4) Issue: 4 Pages: 644-660
  • DOI: 10.1128/mcb.00974-12
  • Peer Reviewed
• [Journal Article] Hoxa9 transduction induces mouse hematopoietic stem and progenitor cell activity through direct down-regulation of Geminin. (2013)
  • Author(s): Ohno, Y., Yasunaga, S., Janmohamed, S., Ohtubo, M., Mihara, K., Iscove, N., Takihara, Y.
  • Journal Title: PLoS ONE Volume: 8(1) Issue: 1 Pages: e53161-e53161
  • DOI: 10.1371/journal.pone.0053161
  • Peer Reviewed
• [Presentation] Negative feed-back loop regulates E2F-mediated transcriptional activation of the Geminin gane (2013)
  • Author(s): Toshiaki Kurogi, Yoshinori Ohno, Shin'ichiro Yasunaga, Kyoko Suzuki-Takedachi, Manabu Shirai, Motoaki Ohtsubo, Yoshihiro Takihara
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
• [Presentation] Negative feed-back loop regulates transcription of the Geminin gene, which governs HSC activity (2013)
  • Author(s): Yoshinori Ohno, Shin'ichiro Yasunaga , Toshiaki Kurogi, Kyoko Suzuki-Takedachi, Yoshie Nakashima, Motoaki Ohtsubo, Yoshihiro Takihara
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌
• [Presentation] E2F-mediated transcriptional activation of the Geminin gene is under the regulation of a negative-feedback loop (2013)
  • Author(s): 大野 芳典
  • Organizer: 第１１回 幹細胞シンポジウム
  • Place of Presentation: 東京大学 伊藤国際学術研究センター
• [Presentation] Negative feed-back loop regulates transcription of the Geminin gene, which governs HSC activity (2013)
  • Author(s): 大野 芳典
  • Organizer: 第７５回 日本血液学会
  • Place of Presentation: 北海道 ロイトン札幌
• [Presentation] Molecular analysis of a role for Geminin in regulating proliferation and differentiation of hematopoietic stem/progenitor cells by visualizing Geminin expression (2013)
  • Author(s): 竹立 恭子
  • Organizer: 第36回 日本分子生物学会
  • Place of Presentation: 兵庫 神戸ポートアイランド
• [Presentation] Scmh1 is required for maintaining hematopoietic homeostasis through the molecular network governing Geminin expression (2012)
  • Author(s): Yoshinori Ohno, Shin'ichiro Yasunaga, Keita Saeki, Motoaki Ohtsubo, Toshiaki kurogi, Yoshie Nakashima, Yoshihiro Takihara
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Repression of Geminin plays an important role in Hoxa9-induced hematopoiesis and leukemogenesis (2012)
  • Author(s): Yoshinori Ohno, Shin'ichiro Yasunaga, Motoaki Ohtsubo, Keita Saeki, Yoshie Nakashima, Yoshihiro Takihara
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会議場
• [Presentation] A new approach for activating mouse hematopoietic stem and progenitor cells by manipulation (2012)
  • Author(s): Yasunaga, S.
  • Organizer: The 10th Stem Cell Research Symposium
  • Place of Presentation: Awaji, Japan
• [Presentation] Scmh1 composes a molecular network regulating Geminin protein to govern hematopoiesis (2012)
  • Author(s): Ohno, Y.
  • Organizer: The 10th Stem Cell Research Symposium
  • Place of Presentation: Awaji, Japan
• [Presentation] Repression of Geminin plays an important role in Hoxa9-induced hematopoiesis and leukemogenesis (2012)
  • Author(s): Ohno, Y.
  • Organizer: The 74th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Kyoto, Japan
• [Presentation] Scmh1 is required for maintaining hematopoietic homeostasis through the molecular network governing Geminin expression (2012)
  • Author(s): Ohno, Y.
  • Organizer: The 35th Annual Meeting of the Molecular Biology of Japan
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Molecular role for Geminin in E2F-mediated transcriptional regulation (2012)
  • Author(s): Saeki K.
  • Organizer: The 35th Annual Meeting of the Molecular Biology of Japan
  • Place of Presentation: Fukuoka, Japan
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/dscb/index.html