Deregulation of Cancer Cell Differentiation and p53 Family GeneSignalin

• Project/Area Number: 17014005
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: IKAWA Shuntaro Tohoku University, 学際科学国際高等研究センター, 准教授 (50241576)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥44,000,000 (Direct Cost: ¥44,000,000); Fiscal Year 2009: ¥8,200,000 (Direct Cost: ¥8,200,000); Fiscal Year 2008: ¥8,200,000 (Direct Cost: ¥8,200,000); Fiscal Year 2007: ¥9,300,000 (Direct Cost: ¥9,300,000); Fiscal Year 2006: ¥9,300,000 (Direct Cost: ¥9,300,000); Fiscal Year 2005: ¥9,000,000 (Direct Cost: ¥9,000,000)
• Keywords: 癌抑制遺伝子 / p53関連遺伝子 / NFκB関連遺伝子 / アポトーシス / 遺伝子治療 / NFκB関連潰云子 / NFkB関連遺伝子 / 転写因子 / 分化 / DNA損傷 / シグナル伝達

Research Abstract

I analyzed p53 family gene, p51, and accomplished following findings. 1)I Identified ubiquitin ligase specific to TAp51 protein. 2)I elucidated mechanisms of cell fate determination in response to genotoxic stress by p53 family proteins, 3)Some p53 family gene chimeras exhibited potent anti-tumor activity by mouse gene therapy model. 4)p51 gene expression is essential for maintaining immaturity (stemness) in keratinocytes and muscle cells.

Research Products

• [Journal Article] Bach1-dependent and -independent regulation of heme oxygenase-1 in keratinocytes (2010)
  • Author(s): Okada, S., Muto, A., Ogawa, E., Nakanome, A., Katoh, Y., Ikawa, S., Aiba, S., Igarashi, K., Okuyama, R.
  • Journal Title: Journal of Biological Chemistry (in press)
  • Peer Reviewed
• [Journal Article] Expression analysis of p51/p63 in enamel organ epithelial cells (2010)
  • Author(s): Matsuura T., Nagoshi H., Tomooka Y., Ikawa S., Sasaki K.
  • Journal Title: Interface oral health science 2009 36 Pages: 133-136
• [Journal Article] Expression analysis of p51/p63 in enamel organ epithelial cells (2010)
  • Author(s): Matsuura T., Nagoshi H., Tomooka Y., Ikawa S., Sasaki K.
  • Journal Title: Interface oral health scienoe 2009 Pages: 133-136
• [Journal Article] Expression analysis of p51/p63 in enamel organ epithelial cells (2009)
  • Author(s): Matsuura T., Nagoshi H., Tomooka Y., Ikawa S., Sasaki K.
  • Journal Title: Journal of Oral Biosciences 36 Pages: 51-58
  • Peer Reviewed
• [Journal Article] Ectopic expression of the p53 homologue p63 is linked to squamous metaplasia in extramammary Paget's disease with invasive adenocarcinoma (2009)
  • Author(s): Okuyama R, Ogawa E, Egawa T, Nagoshi H, Tagami H, Ikawa S, Aiba S.
  • Journal Title: Histopahology 54(2009) Pages: 378-381
  • Peer Reviewed
• [Journal Article] Ectopic expression of the p53 homologue p63 is linked to squamous metaplasia in extramammary Paget's disease with invasive adenocarcinoma (2009)
  • Author(s): Ogawa E, Okuyama R, Egawa T, Nagoshi H, Tagami H, Ikawa S, Aiba S.
  • Journal Title: Histopathology 54 Pages: 378-381
  • Peer Reviewed
• [Journal Article] Expression analysis of p51/p63 in enamel organ epithelial cells (2009)
  • Author(s): Matsuura T., Nagoshi H., Tomooka Y., Ikawa S., Sasaki K.
  • Journal Title: Journal of oral biosciences 36 Pages: 51-58
  • Peer Reviewed
• [Journal Article] Ectopic expression of the p53 homologue p63 is linked to squamous metaplasia in extramammary Paget's disease with invasive adenocarcinoma (2009)
  • Author(s): Ogawa E, Okuyama R, Egawa T, Nagoshi H, Tagami H, Ikawa S, Aiba S
  • Journal Title: Histopathology 54 Pages: 378-81
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): Okuyama R, Ogawa E, Egawa T, Nagoshi H, Obinata M, Tagami H, Ikawa S, Aiba S.
  • Journal Title: Journal of Biological Chemistry 283(2008) Pages: 34241-34249
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): Okuyama R, Ogawa E, Ikawa S, Nagoshi H, Egawa T, Kurihara A, Yabuki M, Tagami H, Obinata M, Aiba S.
  • Journal Title: Oncogene 27 Pages: 848-856
  • Peer Reviewed
• [Journal Article] p63/p51-induced onset of keratinocyte differentiation via the c-Jun N-terminal kinase pathway is counteracted by keratinocyte growth factor (2008)
  • Author(s): Ogawa E, Okuyama R, Egawa T, Na goshi H, Obinata M, Tagami H, Ikawa S, Aiba S
  • Journal Title: J Biol Chem 283 Pages: 34241-9
  • Peer Reviewed
• [Journal Article] p51/p63 Inhibits ultraviolet B-induced apoptosis via Akt activation (2008)
  • Author(s): Ogawa E, Okuyama R, Ikawa S, Nagoshi H, Egawa T, Kurihara A, Yabuki M, Tagami H, Obinata M, Aiba S
  • Journal Title: Oncogene 27 Pages: 848-56
  • Peer Reviewed
• [Journal Article] p51/p63 inhibits ultraviolet B-induced apoptosis via Akt activation. (2008)
  • Author(s): Ogawa, E, Okuyama, R., Ikawa, S., Nagoshi, H., Egawa, T., Kurihara, A., Yabuki, M., Tagami, H., Obinata, M., and, Aiba, S.
  • Journal Title: Oncogene (accepted). (In press)
  • Peer Reviewed
• [Journal Article] Ser46 phosphorylation of p53 is not always sufficient to induce apoptosis: multiple mechanisms of regulation of p53-dependent apoptosis (2007)
  • Author(s): Kurihara, A., Nagoshi, A., Yabuki, M., Okuyama, R., Obinata, M., Ikawa, S.
  • Journal Title: Genes Cells 12 Pages: 853-861
  • Peer Reviewed
• [Journal Article] p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity (2007)
  • Author(s): Okuyama, R., Ogawa, E., Nagoshi, H., Yabuki, M., Kurihara, A., Terui, T., Aiba, S., Obinata, M., Tagami, H., Ikawa, S.
  • Journal Title: Oncogene 26 Pages: 4478-4488
  • Peer Reviewed
• [Journal Article] Ser46 phosphorylation of p53 is not always sufficient to induce apoptosis: multiple mechanisms of regulation of p53-dependent apoptosis. (2007)
  • Author(s): Kurihara A, Nagoshi H, Yabuki M, Okuyama R, Obinata M, Ikawa S.
  • Journal Title: Genes Cells 12(7) Pages: 853-61
  • Peer Reviewed
• [Journal Article] p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity. (2007)
  • Author(s): Okuyama R, Ogawa E, Nagoshi H, Yabuki M, Kurihara A Terui T, Aiba S, Obinata M, Tagami H, Ikawa S.
  • Journal Title: Oncogene 5;26(31) Pages: 4478-88
  • Peer Reviewed
• [Journal Article] p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate (2006)
  • Author(s): Kunisaki, R., Ikawa, S., Maeda, R., Nakazaki, Y., Kurita, R., Harata, M., Shutoh, Y., Bai, S.Y., Tanabe, T., Dohi, T., Kato, R., Ikawa, Y., Sekihara, H., Asano, S., Tani, K
  • Journal Title: J Gene Med 8 Pages: 1120-1130
  • Peer Reviewed
• [Journal Article] p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate. (2006)
  • Author(s): Kunisaki, R., Ikawa, S., Maeda, R., Nakazaki, Y., Kurita, R., Harata, M., Shutoh, Y., Bai, S.Y., Tanabe, T., Dohi, T., Kato, R., Ikawa, Y., Sekihara, H., Asano, S., Tani, K.
  • Journal Title: J Gene Med. 8 Pages: 1120-1130
• [Journal Article] Identification and characterization of Xenopus laevis homologs of mammalian TRAF6 and its binding protein TIFA (2005)
  • Author(s): Inoue, JI., Yagi, S., Ishikawa, K., Azuma, S., Ikawa, S., Semba, K.
  • Journal Title: Gene 358 Pages: 53-59
  • Peer Reviewed
• [Journal Article] Structure and the evolutionary implication of the triplicated complement factor B genes of a urochordate ascidian, Ciona intestinalis (2005)
  • Author(s): Yoshizaki, FY., Ikawa, S., Satake, M., Satoh, N., Nonaka, M.
  • Journal Title: Immunogenetics. Immunogenetics 56 Pages: 930-942
  • Peer Reviewed
• [Journal Article] Identification of DRG family regulatory proteins (DFRPs): specific regulation of DRG1 and DRG2 (2005)
  • Author(s): Ishikawa, K., Azuma, S., Ikawa, S., Semba, K., Inoue, J.
  • Journal Title: Genes Cells 10 Pages: 139-150
  • Peer Reviewed
• [Journal Article] Identification of DRG family regulatory proteins (DFRPs) : specific regulation of DRG1 and DRG2. (2005)
  • Author(s): Ishikawa, K., Azuma, S., Ikawa S., Semba, K., Inoue, J
  • Journal Title: Genes Cells 10 Pages: 139-150
• [Journal Article] Structure and the evolutionary implication of the tripicated complement factor B genes of a urochordate ascidian, Ciona intestinalis. (2005)
  • Author(s): Yoshizaki, FY., Ikawa S., Satake, M., Satoh, N., Nonaka, M
  • Journal Title: Immunogenetics 56 Pages: 930-942
• [Journal Article] Identification and characterization of Xenopus laevis homologs of mammalian TRAF6 and its binding protein TIFA. (2005)
  • Author(s): Inoue, JI., Yagi, S., Ishikawa, K., Azuma, S., Ikawa.S., Semba, K
  • Journal Title: Gene 358 Pages: 53-59
• [Journal Article] Ser46 phosphorylation of p53 is not always sufficient to induce apoptosis : multiple mechanisms of regulation of p53-dependent apoptosis.
  • Author(s): Kurihara, A., Nagoshi, A., Yabuki, M., Okuyama, R., Obinata, M., Ikawa, S.
  • Journal Title: Genes Cell (in press)
• [Journal Article] p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notchl activity.
  • Author(s): Okuyama, R., Ogawa, E., Nagoshi, H., Yabuki, M., Kurihara, A., Terui, T., Aiba, S., Obinata, M., Tagami, H., Ikawa, S.
  • Journal Title: Oncogene (in press)
• [Presentation] Notch2 down-regulation in wound healing is contributed to acceleration of cerll motility (2009)
  • Author(s): 斉藤るみ子、奥山隆平、小川英作、井川俊太郎、饗庭節也
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] 骨格筋分化におけるp53類似遺伝子p51の役割 (2009)
  • Author(s): 小川静香、井川俊太郎、永富良一
  • Organizer: 第64回日本体力医学会大会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-18
• [Presentation] 歯胚発生におけるp51/p63遺伝子の役割 (2009)
  • Author(s): 松裏貴史, 名越弘和, 友岡康弘, 井川俊太郎, 佐々木啓一
  • Organizer: 第51回歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-10
• [Presentation] 筋芽細胞の未分化維持とp53類似遺伝子Δp51の関係 (2008)
  • Author(s): 小川静香
  • Organizer: 第63回日本体力医学会大会
  • Place of Presentation: 別府ビーコンプラザ
• [Presentation] 98th annual meeting of American Association for Cancer Research (2007)
  • Author(s): Nagoshi, H., Ikawa, S.
  • Organizer: 97th annual meeting of American Association for Cancer Research (mini symposium, Ito-en young investigator award)
  • Place of Presentation: Los Angeles, USA
• [Presentation] Cell fate determination by IkB kinase g-p51 ubiquitin ligase-p51 pathway in Response to DNA damaging Stimuli. (2007)
  • Author(s): Nagoshi, H., Ikawa. S.
  • Organizer: 98th annual meeting of American Association for Cancer Research.
  • Place of Presentation: Los Angeles, USA
• [Presentation] Cell Fate Determination by IKK gamma-p53 family pathway in Response to DNA Damaging Stimuli. (2007)
  • Author(s): 名越弘和、栗原祥、矢吹仁人、帯刀益夫、井川俊太郎
  • Organizer: 第66回日本癌学会総会一般口演
  • Place of Presentation: 横浜
• [Presentation] Regulation of Apoptosis by IkB kinase g -p51 ubiquitin ligase - p51pathway in Response to DNA damaging Stimuli (2006)
  • Author(s): Nagosh, H., Ikawa, S.
  • Organizer: 97th annual meeting of American Association for Cancer Research (mini symposium, Ito-en young investigator award)
  • Place of Presentation: Washington DC, USA
• [Presentation] The p53 family gene chimeras: a new resource for potent gene therapy of cancer (2006)
  • Author(s): Yabuki, M., Kaneshiro, K., Nagoshi, H., Kurihara, A., Aburatani, H., Obinata, M., Ikawa, S.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto, Japa
• [Presentation] Mechanisms of Cell Fate Determination in Response to DNA Damage by p53 Family Proteins (2006)
  • Author(s): Kurihara, A., Nagoshi, H., Yabuki, M., Obinata, M., Ikawa, S.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
  • Place of Presentation: Kyoto, Japan
• [Book] 癌とシグナル(編修 佐竹正延、菅原和夫, シグナル伝達病を知る, p 53)(遺伝子医学MOOK) (2006)
  • Author(s): 井川俊太郎
  • Publisher: 株式会社メディカルドウ
• [Book] ファミリーのシグナル伝達による癌抑制のメカニズム(シグナル伝達研究2005-2006, 編修 山本雅/仙波憲太郎, p 53)(実験医学) (2005)
  • Author(s): 井川俊太郎
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.cir.tohoku.ac.jp/j/2research/2007prof.htm#ikawa
• [Remarks]
  • URL: http://www.cir.tohoku.ac.jp/j/2research/2007prof.htm#ikawa
• [Patent(Industrial Property Rights)] p53 ファミリーのキメラ遺伝子及びキメラタンパク (2009)
  • Inventor(s): 井川洋二、井川俊太郎、帯刀益夫
  • Industrial Property Rights Holder: 井川洋二、大塚製薬株式会社
  • Filing Date: 2009-11-06
• [Patent(Industrial Property Rights)] p53ファミリーのキメラ遺伝子及びキメラタンパク (2009)
  • Inventor(s): 井川洋二、井川俊太郎、帯刀益夫
  • Industrial Property Rights Holder: 井川洋二、大塚製薬株式会社
  • Acquisition Date: 2009-11-06