Stress-induced NF-κB mediated by the nuclear IKKβandcelldeath

• Project/Area Number: 23870022
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Hiroshima University
• Principal Investigator: TSUCHIYA Yoshihiro 広島大学, 大学院・医歯薬保健学研究院, 特任助教 (90611301)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: NF-κB / 細胞内シグナル伝達 / ストレス応答 / アダプター / 炎症 / NF-kB / 肝炎 / IKK / 紫外線 / 細胞死 / IKKβ

Research Abstract

We have found that nuclear IKKβ induces IκB degradation in UV- and oxidative stress-induced NF-κB activation. The administration of concanavalin A (ConA) and acetaminophen(APAP) to mice causes cell death and severe liver injury. Expression of IKKβ in the nucleus in IKKβ knockout mice greatly increases ALT levels and exhibited sever liver damage. These results suggested a possible involvement of nuclear IKKβ pathway in hepatitis.

Research Products

• [Journal Article] Role of Pin1 in the pathogenesis of non-alcoholic steatohepatitis in a rodent model (2012)
  • Author(s): Nakatsu Y, Otani Y, Sakoda H, Zhang J, Guo Y, Okubo H, Kushiyama A, Fujishiro M, Kikuchi T, Fukushima T, Ohno H, Tsuchiya Y, Kamata H, Nagamachi A, Inaba T, Nishimura F, Katagiri H, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 287 Issue: 53 Pages: 44526-44535
  • DOI: 10.1074/jbc.m112.397133
  • Peer Reviewed
• [Journal Article] Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes. (2012)
  • Author(s): Iwashita M, Sakoda H, Kushiyama A, Fujishiro M, Ohno H, Nakatsu Y, Fukushima T, Kumamoto S, Tsuchiya Y, Kikuchi T, Kurihara H, Akazawa H, Komuro I, Kamata H, Nishimura F, Asano T.
  • Journal Title: American Journal of Physiology - Endocrinology and Metabolism Volume: 302 Issue: 3 Pages: 286-296
  • DOI: 10.1152/ajpendo.00324.2011
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 286 Issue: 23 Pages: 20812-20822
  • DOI: 10.1074/jbc.m110.206904
  • Peer Reviewed
• [Presentation] IKKβの脱リン酸化反応における転写因子RelAの関与 (2012)
  • Author(s): 土谷佳弘, 金本麻裕, 菅野雅元, 浅野知一郎, 鎌田英明
  • Organizer: 第85回日本生化学会合同大会ワークショップ
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-16
• [Presentation] Stress-induced NF-kB activation mediated by the nuclear IKK and cell death (2012)
  • Author(s): 土谷佳弘, 金本麻裕, 菅野雅元, 浅野知一郎, 鎌田英明
  • Organizer: 35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] Nuclear IKKβ acts as an adaptor protein for IκBα ubiquitination and degradation in UV- and oxidative stress-induced NF-κB activation. Keystone Symposium (2012)
  • Author(s): Yoshihiro Tsuchiya, Tomoichiro Asano, Keiko Nakayama, Tomohisa Kato, Jr., Michael Karin, and Hideaki Kamata
  • Organizer: NF-kappaB Signaling and Biology: From Bench to Bedside
  • Place of Presentation: Whistler, British Columbia, Canada
  • Year and Date: 2012-03-25
• [Presentation] Stress-induced NF-kB activation mediated by the nuclear IKK and cell death (2012)
  • Author(s): 土谷佳弘
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] 腫瘍壊死因子(TNFα)に応答した細胞死とRIP1とRIP3の発現変化 (2012)
  • Author(s): 金本麻裕
  • Organizer: 第85回日本生化学会合同大会
  • Place of Presentation: 福岡
• [Presentation] IKKβの多重的活性制御機構ー転写因子p65 によるネガティブフィードバックとレドックス制御の関与 (2011)
  • Author(s): 土谷佳弘, 浅野知一郎, 菅野雅元,鎌田英明
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] IKKbetaの多重的活性制御機構-転写因子p65によるネガティブフィードバックとレドックス制御の関与 (2011)
  • Author(s): 土谷佳弘
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-16
• [Presentation] IKKβ act as an adaptor protein for IκBα ubiquitination and degradation in UV-induced NF-κB activation; possible involvement in the TNF signaling (2011)
  • Author(s): Yoshihiro Tsuchiya a n d H i d e a k i K a m a t a
  • Organizer: 13th International TNF Conference
  • Place of Presentation: Awajishima
  • Year and Date: 2011-05-17
• [Presentation] IKKβ act as an adaptor protein for IκBα ubiquitination and degradation in UV-induced NF-κB activation ; possible involvement in the TNF sign aling (2011)
  • Author(s): Yoshihiro Tsuchiya
  • Organizer: 13th International TNF Conference
  • Place of Presentation: 淡路
  • Year and Date: 2011-05-17
• [Remarks] ホームページ
  • URL: http://home.hiroshima-u.ac.jp/ikagaku/index.html
• [Remarks] 受賞 2012年12月 第85回日本生化学会合同大会 鈴木紘一メモリアル賞