| Project/Area Number |
14570490
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nagoya City University |
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Principal Investigator |
TAKASHI Joh (2003) Nagoya City University, Graduate School of Medical Sciences, Associate Proffesor., 大学院・医学研究科, 助教授 (30231369)
妹尾 恭司 (2002) 名古屋市立大学, 大学院・医学研究科, 助手 (30295589)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Makoto Nagoya City University, Graduate School of Medical Sciences, Proffesor, 大学院・医学研究科, 教授 (40217774)
城 卓志 名古屋市立大学, 大学院・医学研究科, 助教授 (30231369)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | NAP1 / NF-κB / TNF-α / NAK / Gastritis / Inflammatory Bowel Disease / Transcription Factor / Molecular Mechanism / 炎症性腸疾息 / IKK / NAKBP |
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| Research Abstract |
The IκB kinase (IKK)-related kinase NAK (also known as TBK or T2K) contributes to the activation of NF-κB-dependent gene expression. Here we identify NAP1 (for NAK-associated protein 1), a protein that interacts with NAK and its relative IKKε(also known as IKKi). NAP1 activates NAK and facilitates its oligomerization. Interestingly, the NAK-NAP1 complex itself effectively phosphorylated serine 536 of the p65/RelA subunit of NF-κB, and this activity was stimulated by tumor necrosis factor alpha (TNF-α).
Overexpression of NAP1 specifically enhanced cytokine induction of an NF-κB-dependent reporter gene expression and sensitized cells to TNF-α-induced apoptosis. These results define NAP1 as an activator of IKKK-related kinases and suggest that the NAK-NAP1 complex may protect cells from TNF-α-induced apoptosis by promoting NF-κB activation.
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