Involvement of NF-kB regulation by nuclear IKKb in inflammation and cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 23370062
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Hiroshima University
• Principal Investigator: KAMATA Hideaki 広島大学, 医歯薬保健学研究院, 准教授 (10233925)
• Co-Investigator(Renkei-kenkyūsha): SOTOMARU Yusuke 広島大学, 自然科学研究支援開発センター, 教授 (90309352)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: NF-κB / IKK / 細胞質 / 核 / 炎症 / 発がん

Outline of Final Research Achievements

Proinflammatory stimuli, including tumor necrosis factor α (TNFα), activate IκB kinase (IKK) complex and induces NF-κ activation. We previously found that nuclear IKKβ acts as an adaptor protein for IκBα degradation and NF-κB activation. To elucidate the role of IKKβ in vivo, we developed mice expressing nuclear-localized IKKβ and lacking cytoplasmic IKKβ in hepatocytes. These mice showed massive hepatic necrosis and developed liver cirrhosis. Whereas, liver failure of these mice was ameliorated by crossing with mice expressing cytoplasmic-localized IKKβ. These results suggest that nuclear IKKβ promote cell death and cytoplasmic IKKβ protect cells from death in vivo. The opposite effect of IKKβ in the nucleus and cytoplasm is closely linked to hepatitis and hepatocellular carcinoma.

Free Research Field

医化学