| Project/Area Number |
24791980
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional basic dentistry
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| Research Institution | Fukuoka Dental College (2013)
Kyushu Dental College (2012) |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 破骨細胞 / ユビキチン化 / プロテアソーム / SCF型ユビキチンリガーゼ / NF-kB / FBW7 / b-TRCP / 骨代謝 / 骨 / RANKL / RANK / ユビキチン / タンパク質分解 |
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| Research Abstract |
Ubiquitin-Proteasome pathway has been recently shown to influence osteoclast formation and function, the precise molecular cascade underlying these effects is presently unclear. Recent our studies showed that b-TRCP induced processing of NFkB2/p100 to p52 is the critical step in activation of RANKL induced alternative NF-kB signaling pathway. This processing event is triggered by NIK-IKKa induced phosphorylation of NFkB2. In this study, we found novel activation mechanism of b-TRCP induced NFkB2/p100 processing pathway via Akt/Cot-IKKa activation. Furthermore, we identified Fbw7 as a physiological E3 ligase controlling NFkB2/p100's stability. It further implicates that Fbw7 might exert osteoclast differentiation by regulating NF-kB activity. These results suggested that NFkB2 is the unique molecule regulated by multiple ubiquitin proteasomal pathways in osteoclast differentiation.
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