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

2008 Fiscal Year Final Research Report

• 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
• Keywords: 口腔生化学

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] 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] 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
• [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
• [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
  • Year and Date: 20090322-27
• [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
  • Year and Date: 20081209-12
• [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
  • Year and Date: 20081112-14
• [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
  • Year and Date: 20080713-18
• [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
  • Year and Date: 20080214-15
• [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
  • Year and Date: 20070829-31
• [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
  • Year and Date: 20070707-12
• [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)