Cell fate decision mechanism by the transcription factor E2F in cell growth and tumor suppression

• Project/Area Number: 21570180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kwansei Gakuin University
• Principal Investigator: OHTANI Kiyoshi 関西学院大学, 理工学部, 教授 (30201974)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 細胞増殖 / 癌化抑制 / 細胞運命 / 転写因子 / アポトーシス / E2F / PI3キナーゼ / microRNA / p53

Research Abstract

We analyzed the molecular mechanism of control of cell growth and tumor suppression mediated by the transcription factor E2F, the main target of the tumor suppressor pRB. We identified 5 novel genes, which are specifically activated by E2F induced by loss of pRB function, a representative oncogenic change. Many of these gene products are involved in the p53 pathway, which induces cell death. PI3 kinase pathway did not suppress activation of tumor suppressor genes by E2F induced by loss of pRB function.

Research Products

• [Journal Article] Inability of p53-reactivating compounds Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient in p53Ser46 phosphorylation (2012)
  • Author(s): Ma, T., Yamada, S., Ichwan, S., Iseki, S., Ohtani, K., Otsu, M., Ikeda, MA.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: (in press)
  • Peer Reviewed
• [Journal Article] Inability of p53-reactivating compounds Nutlin-3 and RITA to overcome p53 resistance in tumor cells deficient in p53Ser46 phosphorylation (2012)
  • Author(s): Ma, T.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential. (2011)
  • Author(s): Ohno, Y.
  • Journal Title: Proc Natl Acad Sci USA Volume: (In press)
  • Peer Reviewed
• [Journal Article] Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential (2010)
  • Author(s): Ohno, Y., Yasunaga, S., Ohtsubo, M., Mori, S., Tsumura, M., Okada, S., Ohta, T., Ohtani, K., Kobayashi, M., and Takihara, Y.
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 21529-21534
  • Peer Reviewed
• [Journal Article] E2F-like elements in p27Kip1 promoter specifically sense deregulated E2F activity (2009)
  • Author(s): Ozono, E., Komori, H., Iwanaga, R., Ikeda, MA., Iseki, S., and Ohtani, K.
  • Journal Title: Genes Cells Volume: 14 Pages: 89-99
  • Peer Reviewed
• [Journal Article] E2F-like elements in p27^<Kip1> promoter specifically sense deregulated E2F activity (2009)
  • Author(s): Eiko Ozono
  • Journal Title: Genes Cells 14 Pages: 89-99
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 大谷清(共著)
  • Journal Title: 染色体サイクル(共立出版)
• [Presentation] Identification of novel target genes that are specifically activated by deregulated E2F (2011)
  • Author(s): Kitamura, H.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] The tumor suppressor ARF gene specifically senses deregulated E2F activity through multiple atypical E2F-responsive elements (2011)
  • Author(s): Onishi, R.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Identification of novel target genes that are specifically activated by deregulated E2F (2011)
  • Author(s): Kitamura, H.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] The tumor suppressor ARF gene specifically senses deregulated E2F activity through multiple atypical E2F-responsive elements (2011)
  • Author(s): Onishi, R.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-14
• [Presentation] Cancer cell lines, but not normal growing fibroblasts, harbor deregulated E2F activity that activates the tumor suppressor TAp73 gene (2011)
  • Author(s): Ozono, E.
  • Organizer: 7th NCRI Cancer Conference
  • Place of Presentation: Liverpool, UK
  • Year and Date: 2011-11-08
• [Presentation] Identification of novel genes that are specifically activated by deregulated E2F (2011)
  • Author(s): Ozono, E.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Identification of novel genes that are specifically activated by deregulated E2F (2011)
  • Author(s): Ozono, E.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] RB1-deficient cancer cells specifically harbor deregulated E2F activity that activates the tumor suppressor p73 gene (2011)
  • Author(s): Ozono, E.
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-28
• [Presentation] RB1-deficient cancer cells specifically harbor deregulated E2F activity that activates the tumor suppressor p73 gene (2011)
  • Author(s): Ozono, E.
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学クラーク会館学術交流会館
  • Year and Date: 2011-06-28
• [Presentation] Activation of the CDK7 gene by the oncogene product Tax of HTLV-I (2010)
  • Author(s): Kurahashi, Y.
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Identification of a histone methyltransferase gene as a new target for the trans-activator protein Tax of HTLV-I (2010)
  • Author(s): Konishi, T.
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Activation of the CDK7 gene by the oncogene product Tax of HTLV-I (2010)
  • Author(s): Kurahashi, Y.
  • Organizer: 第33回 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-09
• [Presentation] Identification of a histone methyltransferase gene as a new target for the trans-activator protein Tax of HTLV-I (2010)
  • Author(s): Konishi, T.
  • Organizer: 第33回 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-09
• [Presentation] Identification new E2F target genes specifically activated by loss of pRB function (2010)
  • Author(s): Kugawa, K.
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Effect of Nutlin-3 on p53 resistance in tumor cells lacking the ability to phosphorylate Ser46 on p53 (2010)
  • Author(s): Ma, T.
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Cancer cell lines, but not normal cells, harbor deregulated E2F activity that activates the tumor suppressor p73 gene (2010)
  • Author(s): Ozono, E.
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Identification new E2F target genes specifically activated by loss of pRB function (2010)
  • Author(s): Kugawa, K.
  • Organizer: 第33回 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] Effect of Nutlin-3 on p53 resistance in tumor cells lacking the ability to phosphorylate Ser46 on p53 (2010)
  • Author(s): Ma, T.
  • Organizer: 第33回 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] Cancer cell lines, but not normal cells, harbor deregulated E2F activity that activates the tumor suppressor p73 gene (2010)
  • Author(s): Ozono, E.
  • Organizer: 第33回 日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] Cancer cell lines, but not normal cells, harbor deregulated E2F activity that activates tumor suppressor genes (2010)
  • Author(s): Ozono, E.
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Cancer cell lines, but not normal cells, harbor deregulated E2F activity that activates tumor suppressor genes (2010)
  • Author(s): Ozono, E.
  • Organizer: 第69回 日本癌学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-23
• [Presentation] RB-deficient cancer cells have deregulated E2F activity that activates tumor suppressor genes (2009)
  • Author(s): Ozono, E.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] Cell type-specific effect of HTLV-I Tax (2009)
  • Author(s): Ohtani, K.
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] The tumor suppressor p73 gene is preferentially activated by deregulated E2F (2009)
  • Author(s): Ozono, E.
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Book] Therapeutic Targeting of p53-mediated Apoptosis Pathway in Head and Neck Squamous Cell Carcinomas : Current Progress and Challenges. in "Tumor Suppressor Genes" (2012)
  • Author(s): Ichwan, S., Bakhtiar, MT., Ohtani, K. and Ikeda, MA. Yue Cheng
  • Total Pages: 16
  • Publisher: InTech Open Access Publisher
• [Book] Tumor Suppressor Genes (2012)
  • Author(s): Ichwan, S.
  • Publisher: InTech Open Access Publisher
• [Book] 染色体DNAの複製と安定性を司るRB/E2F-蛋白質・核酸・酵素 (2009)
  • Author(s): 大谷清、大園瑛子
  • Total Pages: 7
• [Remarks]