| Project/Area Number |
13557043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | Nagoya City University |
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Principal Investigator |
NAKANISHI Makoto Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (40217774)
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| Co-Investigator(Kenkyū-buntansha) |
FURUTA Kyoji Gifu University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (40173538)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2001: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | Inflammation / NF-kB / Prostaglandin / IKK / NAK / NAP1 / apoptosis / TNF-α / NF-KB |
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| Research Abstract |
The IKK-related kinase NAK contributes to the activation of NF-κB-dependent gene transcription. Here we identify NAP1 (NAK-associated protein 1), a protein that interacts with NAK and its relative IKKε. 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-α (TNF-α). Overexpression of NAP1 specifically enhanced cytokine-induction of an NF-κB-dependent, but not AP-1-dependent reporter. Depletion of NAP1 reduced NF-κB-dependent gene expression and sensitized cells to TNF-α-induced apoptosis. These results define NAP1 as an activator of IKK-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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