Role of Ubiquitin-Proteasome System in Osteoclast Differentiation
Project/Area Number |
24791980
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Functional basic dentistry
|
Research Institution | Fukuoka Dental College (2013) Kyushu Dental College (2012) |
Principal Investigator |
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Project Period (FY) |
2012-04-01 – 2014-03-31
|
Project Status |
Completed (Fiscal Year 2013)
|
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)
|
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 |
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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Report
(3 results)
Research Products
(32 results)
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[Journal Article] RelB-induced Expression of Cot, an MAP3K Family Member, Rescues RANKL-induced Osteoclastogenesis in Alymphoplasia Mice by Promoting NF-κB2 Processing by IKKα.2014
Author(s)
Taniguchi R, Fukushima H, Osawa K, Maruyama T, Yasuda H, Weih F, Doi T, Maki K, Jimi E.
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Journal Title
J Biol Chem.
Volume: 289
Issue: 11
Pages: 7349-7361
DOI
Related Report
Peer Reviewed
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[Journal Article] SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression.2013
Author(s)
Fukushima H, Ogura K, Wan L, Lu Y, Li V, Gao D, Liu P, Lau AW, Wu T, Kirschner MW, Inuzuka H, Wei W.
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Journal Title
Cell Rep.
Volume: 4
Issue: 4
Pages: 803-816
DOI
Related Report
Peer Reviewed
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[Journal Article] p130Cas plays important roles in osteoclastic bone resorption2013
Author(s)
Nagai Y, Osawa k, Fukushima H, Tamura Y, Aoki K, Ohya K, Yasuda H, Hikiji H, Kato S, Honda H, Nakamura I, Maki K, Jimi E
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Journal Title
J. Bone Miner. Res
Volume: 28
Issue: 12
Pages: 2449-2462
DOI
Related Report
Peer Reviewed
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[Journal Article] Disruption of NF-κB1 prevents bone loss caused by mechanical unloading.2013
Author(s)
Nakamura H, Aoki K, Masuda W, Alles N, Nagano K, Fukushima H, Osawa K, Yasuda H, Nakamura I, Mikuni-Takagaki Y, Ohya K, Maki K, Jimi E.
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Journal Title
J Bone Miner Res.
Volume: 28
Issue: 6
Pages: 1457-1467
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Acetylation-dependent regulation of Skp2 function2012
Author(s)
Inuzuka H, Gao D, Finley LW, Yang W, Wan L, Fukushima H, Chin YR, Zhai B, Shaik S, Lau AW, Wang Z, Gygi SP, Nakayama K, Teruya-Feldstein J, Toker A, Haigis MC, Pandolfi PP, Wei W
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Journal Title
Cell
Volume: 150(1)
Issue: 1
Pages: 179-93
DOI
Related Report
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[Journal Article] SCF(β-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 22012
Author(s)
Shaik S, Nucera C, Inuzuka H, Gao D, Garnaas M, Frechette G, Harris L, Wan L, Fukushima H, Husain A, Nose V, Fadda G, Sadow PM, Goessling W, North T, Lawler J, Wei W
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Journal Title
J Exp Med
Volume: 209
Issue: 7
Pages: 1289-307
DOI
Related Report
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[Journal Article] SCF(Fbw7) modulates the NFkB signaling pathway by targeting NFkB2 for ubiquitination and destruction2012
Author(s)
Fukushima H, Matsumoto A, Inuzuka H, Zhai B, Lau AW, Wan L, Gao D, Shaik S, Yuan M, Gygi SP, Jimi E, Asara JM, Nakayama K, Nakayama KI, Wei W
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Journal Title
Cell Rep
Volume: 1
Pages: 434-43
Related Report
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