Activation mechanism and physiological role of the ATM checkpoint kinase in response to oxidative stress

• Project/Area Number: 22710052
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kanazawa University
• Principal Investigator: KOBAYASHI Masahiko 金沢大学, がん進展制御研究所, 助教 (70285633)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 応答 / ATM / 酸化ストレス / 老化 / 細胞応答 / 代謝産物

Research Abstract

The sulfhydryl-reactive oxidative stress agents 15d-PGJ_2, ONE and 8-nitro-cGMP induce phosphorylation and accumulation of p53 and apoptosis but DNA damage response. The ATM activation by 15d-PGJ_2 does not require a disulfide-cross-linked dimer formation of ATM, unlike the case by hydrogen peroxide. 15d-PGJ_2 affects the ATM-dependent metabolic regulation. These results obtained in this study characterize the mechanism of the ATM-dependent oxidative stress response that is different from DNA damage response and indicate involvement of the oxidative stress response in regulation of the metabolic system.

Research Products

• [Journal Article] ATR-ATRIP Kinase Complex Triggers Activation of the Fanconi Anemia DNA Repair Pathway (2012)
  • Author(s): Tomoko Shigechi, Junya Tomida, Koichi Sato, Masahiko Kobayashi, John K.Eykelenboom, Fabio Pessina, Yanbin Zhang, Emi Uchida, Masamichi Ishiai, Noel F.Lowndes, Kenichi Yamamoto, Hitoshi Kurumizaka, Yoshihiko Maehara, Minoru Takata
  • Journal Title: Cancer Research Volume: 72 Issue: 5 Pages: 1149-1156
  • DOI: 10.1158/0008-5472.can-11-2904
  • Peer Reviewed
• [Journal Article] Functional relationship between Claspin and Rad17 (2011)
  • Author(s): Yoshimura, A., Akita, M., Hosono, Y., Abe, T., Kobayashi, M., Yamamoto, K.I., Tada, S., Seki, M., Enomoto, T.
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 414 Issue: 2 Pages: 298-303
  • DOI: 10.1016/j.bbrc.2011.09.037
  • Peer Reviewed
• [Journal Article] Dual Functions of ASCIZ in the DNA Base Damage Response and Pulmonary Organogenesis (2010)
  • Author(s): Jurado S, Smyth I, van Denderen B, Tenis N, Hammet A, Hewitt K, Ng JL, McNees CJ, Kozlov SV, Oka H, Kobayashi M, Conlan LA, Cole TJ, Yamamoto K, Taniguchi Y, Takeda S, Lavin MF, and Heierhorst J
  • Journal Title: PLoS Genetics Volume: 6 Issue: 10 Pages: e1001170-e1001170
  • DOI: 10.1371/journal.pgen.1001170
  • Peer Reviewed
• [Presentation] DNA複製チェックポイントにおけるNBS1の役割 (2011)
  • Author(s): 小林昌彦,林直之,山本健一
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-03
• [Presentation] A role for NBS1 in DNA replication checkpoint (2011)
  • Author(s): 小林昌彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-10-03
• [Presentation] Arole for NBS1 in ATR activation (2011)
  • Author(s): Kobayashi M, Hayashi N, Yamamoto K
  • Organizer: 日本分子生物学会・第11回春季シンポジウム・金沢国際がん生物学シンポジウム
  • Place of Presentation: KKRホテル金沢(石川県)
  • Year and Date: 2011-05-26
• [Presentation] A role for NBS1 in ATR activation (2011)
  • Author(s): 小林昌彦
  • Organizer: 日本分子生物学会第11回春季シンポジウム
  • Place of Presentation: KKRホテル金沢(石川県)
  • Year and Date: 2011-05-26
• [Presentation] SH基反応性代謝産物によるATMの活性化 (2010)
  • Author(s): 小林昌彦,林直之,山本健一
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場・リーガロイヤルホテル(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] SH基反応性代謝産物によるATMの活性化 (2010)
  • Author(s): 小林昌彦
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] Arole for NBS1 in ATR activation, Molecular and Cellular Targets for Cancer, Infectious Diseases and Regeneration (2010)
  • Author(s): Kobayashi M, Hayashi N, Yamamoto K
  • Organizer: The Joint Symposium of the 5th International Symposium of Institute Network and The International Symposium Commemorating Inauguration of Kanazawa University Cancer Research Institute
  • Place of Presentation: KKRホテル金沢(石川県)
  • Year and Date: 2010-06-24
• [Presentation] A role for NBS1 in ATR activation (2010)
  • Author(s): 小林昌彦
  • Organizer: The Joint Symposium of the 5th International Symposium of Institute Network
  • Place of Presentation: KKRホテル金沢(石川県)
  • Year and Date: 2010-06-24