Functional analysis of ASK2, a novel stress-responsive kinase, in carcinogenesis of oral squamous cell carcinomas

• Project/Area Number: 19390470
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: TAKEDA Kohsuke The University of Tokyo, 大学院・薬学系研究科, 准教授 (10313230)
• Co-Investigator(Kenkyū-buntansha): NOGUCHI Takuya 東京大学, 大学院・薬学系研究科, 助教 (20431893)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2007: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: 口腔生化学 / 発癌 / MAPキナーゼ / ストレス / アポトーシス / 炎症

Research Abstract

口腔領域の悪性腫瘍の大半を占める口腔扁平上皮癌については、診断ならびに治療法が着実に進歩しているものの、癌細胞の悪性度や抗癌剤に対する感受性などの多様性がいまだに治療の大きな障壁となっている。また、発癌機構についても不明な点が多く残されている。われわれは本研究において、ノックアウトマウスならびにマウス由来培養細胞を用いた解析により、新規ストレス応答キナーゼASK2が癌の抑制に働く機構を明らかにした。

Research Products

• [Journal Article] Stress-activated MAP kinase cascades in cellular senescence. (2009)
  • Author(s): Maruyama, J., Naguro, I., Takeda, K. and Ichijo, H.
  • Journal Title: Curr. Med. Chem. (review article) 16 Pages: 1229-1235
• [Journal Article] Signaling pathways in invertebrate immune and stress response. (2009)
  • Author(s): Hatanaka, R., Sekine, Y., Hayakawa, T., Takeda, K. and Ichijo, H.
  • Journal Title: Invertebrate Survival Journal (review article) 6 Pages: 32-43
• [Journal Article] ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis. (2009)
  • Author(s): Iriyama, T., Takeda, K., Nakamura, H., Morimoto, Y., Kuroiwa, T., Mizukami, J., Umeda, T., Noguchi, T., Naguro, I., Nishitoh, H., Saegusa, K., Tobiume, K., Homma, T., Shimada, Y., Tsuda, H., Aiko, S., Imoto, I., Inazawa, J., Chida, K., Kamei, Y., Kozuma, S., Taketani, Y., Matsuzawa, A. and Ichijo, H.
  • Journal Title: EMBO J. 28 Pages: 843-853
• [Journal Article] USP14inhibits ER-associated degradation via interactionwith IREα. (2009)
  • Author(s): Nagai, A., Kadowaki, H., Maruyama, T., Takeda, K., Nishitoh, H. and Ichijo, H.
  • Journal Title: Biochem. Biophys. Res. Commun. 379 Pages: 995-1000
• [Journal Article] Signaling pathways in invertebrate immune and stress response. (2009)
  • Author(s): Hatanaka, R. et al.
  • Journal Title: Invertebrate Survial Journal 6 Pages: 32-43
  • Peer Reviewed
• [Journal Article] Stress-Activated MAP Kinase Cascades in Cellular Senescence. (2009)
  • Author(s): Maruyama, J. et al.
  • Journal Title: Curr. Med. Chem. 16 Pages: 1229-1235
  • Peer Reviewed
• [Journal Article] ASK1 and ASK2, differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis. (2009)
  • Author(s): Iriyama, T. et al.
  • Journal Title: EMBO J., 28 Pages: 843-853
  • Peer Reviewed
• [Journal Article] USP14 inhibits ER-associated degradation viainteraction with IRE1alpha. (2009)
  • Author(s): Nagai, A. et al.
  • Journal Title: Biochem. Biophys. Res. Commum., 379 Pages: 995-1000
  • Peer Reviewed
• [Journal Article] ALS-linked mutant SOD1 induces ER stress-and ASK1-dependent motor neuron death by targeting Derlin-1. (2008)
  • Author(s): Nishitoh, H., Kadowaki, H., Nagai, A., Maruyama, T., Yokota, T., Fukutomi, H., Noguchi, T., Matsuzawa, A., Takeda, K. and Ichijo, H.
  • Journal Title: Genes Dev. 22 Pages: 1451-1464
• [Journal Article] Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAP kinase pathway for extracellular ATP-induced apoptosis in macrophage. (2008)
  • Author(s): Noguchi, T., Ishii, K., Fukutomi, H., Naguro, I., Matsuzawa, A., Takeda, K. and Ichijo, H.
  • Journal Title: J.Biol.Chem 283 Pages: 7657-7665
• [Journal Article] Apoptosis signal-regulating kinase 1 in stress and immune response. (2008)
  • Author(s): Takeda, K., Noguchi, T., Naguro, I.. and Ichijo, H.
  • Journal Title: Annu. Rev. Pharmacol. Toxicol. (review article) 48 Pages: 199-225
• [Journal Article] ALS-linked mutant SOD1 induces ER stress-and ASK1 dependent motorneuron death by targeting Derlin-1. (2008)
  • Author(s): Nishitoh, H. et al.
  • Journal Title: Genes Dev. 22 Pages: 1451-1464
  • Peer Reviewed
• [Journal Article] Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAP kinase pathway for extracelluler ATP induced apoptosis in imacrophage. (2008)
  • Author(s): Noguchi, T. et al.
  • Journal Title: J. Biol. Chem. 283 Pages: 7657-7665
  • Peer Reviewed
• [Journal Article] Apoptosis Signal-regulating Kinase 1 (ASK1) in stress and immune response. (2008)
  • Author(s): Takeda, K. et al.
  • Journal Title: Annu. Rev. Pharmacol. Toxicol. 48 Pages: 199-225
  • Peer Reviewed
• [Journal Article] Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAP kinase pathway for extracelluler ATP-induced aotosis in macrohage (2008)
  • Author(s): Noguchi, T., et. al.
  • Journal Title: J. Biol. Chem. 283 Pages: 7657-7665
  • Peer Reviewed
• [Journal Article] Apoptosis Signal-regulating Kinase l(ASKl) in stress and immune resonse (2008)
  • Author(s): Takeda, K., et. al.
  • Journal Title: Annu. Rev. Pharmacol. Toxicol. 48 Pages: 199-225
  • Peer Reviewed
• [Journal Article] Thioredoxin and TRAF family proteins regulate ROS-dependent activation of ASK1 through reciprocal modulation of the N-terminal homophilic interaction of ASK1. (2007)
  • Author(s): Fujino, G., Noguchi, T., Matsuzawa, A., Yamauchi, S., Saitoh, M., Takeda, K. and Ichijo, H.
  • Journal Title: Mol. Cell. Biol. 27 Pages: 8152-8163
• [Journal Article] ASKfamily proteins in stress response and disease. (2007)
  • Author(s): Fujisawa, T., Takeda, K. and Ichijo, H.,
  • Journal Title: Mol. Biotechnol.(review article) 37 Pages: 13-18
• [Journal Article] Stress signaling in cancer. (2007)
  • Author(s): Murakami, S., Noguchi, T., Takeda, K. and Ichijo, H.
  • Journal Title: Cancer Sci. (review article) 98 Pages: 1521-1527
  • NAID: 10019997099
• [Journal Article] Chk2 kinase is required for methylglyoxal-induced G2/M cell-cycle checkpoint arrest : implication of cell-cycle checkpoint regulation in diabetic oxidative stress signaling. (2007)
  • Author(s): Kani, S., Nakayama, E., Yoda, A., Onishi, N., Sougawa, N., Hazaka, Y., Umeda, T., Takeda, K., Ichijo, H., Hamada, Y. and Minami, Y
  • Journal Title: Genes Cells 12 Pages: 919-928
• [Journal Article] ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds. (2007)
  • Author(s): Osaka, N., Takahashi, T., Murakami, S., Matsuzawa, A., Noguchi, T., Fujiwara, T., Aburatani, H., Moriyama, K., Takeda, K. and Ichijo, H.
  • Journal Title: J. Cell Biol. 176 Pages: 903-909
• [Journal Article] Apoptosis signal-regulating kinase 2 (ASK2) functions as a MAP3K in a heteromeric complex with ASK1. (2007)
  • Author(s): Takeda, K., Shimozono, R., Noguchi, T., Umeda, T., Morimoto, Y., Naguro, I., Tobiume, K., Saitoh, M., Matsuzawa, A. and Ichijo, H.
  • Journal Title: J.Biol.Chem. 282 Pages: 7522-7531
• [Journal Article] GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. (2007)
  • Author(s): Ito, G., Okai, T., Fujino, G., Takeda, K., Ichijo, H., Katada, T. and Iwatsubo, T.
  • Journal Title: Biochemistry 46 Pages: 1380-1388
• [Journal Article] Pathophysiological roles of ASK1-MAP kinase signaling pathways. (2007)
  • Author(s): Nagai, H., Noguchi, T., Takeda, K. and Ichijo, H.
  • Journal Title: J. Biochem. Mol.Biol.(review article) 40 Pages: 1-6
• [Journal Article] Stress signaling in cancer (2007)
  • Author(s): Murakami, S., et. al.
  • Journal Title: Cancer Sci 98 Pages: 1521-1527
  • Peer Reviewed
• [Presentation] Roles of NSY-1, a C. elegans ortholog of ASK family kinases, in anoxic response. (2009)
  • Author(s): Takeda, K., et al.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology
  • Place of Presentation: Canada
• [Presentation] PGAM5 is a novel serine/threonine protein phosphatase that activates ASK1 (2009)
  • Author(s): Takeda, K. et-al.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology
  • Place of Presentation: Canada
• [Presentation] PGAM5 is a novel serine/threonine protein phosphatase that activates ASK1. (2008)
  • Author(s): Takeda, K., et al.
  • Organizer: 8^<th> International Conference on Protein Phosphatases
  • Place of Presentation: Gunma,Japan
• [Presentation] PGAM5 is a novel serine/threonine protein phosphatase that activates ASK1. (2008)
  • Author(s): Takeda, K., et al.
  • Organizer: FASEB Summer Research Conferences-Protein Phosphatases-
  • Place of Presentation: Colorado, USA
• [Presentation] Stress response by the ASK family kinases and their roles in tumorigenesis. (2008)
  • Author(s): Takeda, K., et al
  • Organizer: CNU symposium on Microbiology and Molecular Genetics
  • Place of Presentation: Korea
• [Presentation] ASK1の活性と機能の新たな制御機構 (2008)
  • Author(s): 武田弘資, 一條秀憲
  • Organizer: BMB2008第31回日本分子生物学会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] PGAM5 is a novel serine/threonine protein phosphatase that activates ASK1 (2008)
  • Author(s): Takeda, K. et al.
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: USA, Colorado
• [Presentation] ASK1の活性と機能の新たな制御機構(シンポジウム) (2008)
  • Author(s): 武田弘資, 一條秀憲
  • Organizer: BMB2008第31回日本分子生物学会年会 第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Stress response by the ASK family kinases and their roles in tumorigenesis (2008)
  • Author(s): Kohsuke Takeda, et. al.
  • Organizer: CNU symposium on Microbiology and Molecular Genetics
  • Place of Presentation: Korea
• [Presentation] Roles of apoptosis signal-regulating kinase 2 (ASK2) in skin tumorigenesis. (2007)
  • Author(s): Takeda, K., et al.
  • Organizer: FASEB Summer Research Conferences-Protein Kinases and Protein Phosphorylation-
  • Place of Presentation: California, USA
• [Presentation] ASKファミリー分子によるストレス応答と発癌機構 (2007)
  • Author(s): 武田弘資
  • Place of Presentation: 札幌
• [Presentation] Roles of apoptosis signal-regulating kinase2(ASK2)in skinn tumorteneses (2007)
  • Author(s): Takeda、K., et. al.
  • Organizer: FASEB Summer Research Conferences-Protein Kinases and Protein Phosholation-
  • Place of Presentation: califonia,USA
• [Presentation] ASKファミリー分子によるストレス応答と発癌機構 (2007)
  • Author(s): 武田 弘資
  • Organizer: 第49回歯科基礎医学会学術大会・総会
  • Place of Presentation: 札幌
• [Book] 細胞死とアポトーシス制御機構 (2008)
  • Author(s): 武田弘資, 一條秀憲
  • Publisher: 「口腔内科学」飛鳥出版室(尾崎登喜雄)