Functional analysis of complex type ubiquitin ligase
| Project/Area Number |
18370076
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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 | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Nagoya University |
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Principal Investigator |
KAMURA Takumi Nagoya University, Graduate School of Science, Professor (40333455)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,620,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Ubiouitin / protein degradation |
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| Research Abstract |
Ubiquitylation and subsequent proteasomal degradation of regulatory proteins control a variety of cellular processes, including cell cycle progression, gene transcription, and signal transduction. The ubiquitin conjugation to target proteins is processed by three enzymes, El, E2, and E3. The E3s are responsible for recognizing and recruiting target proteins for polyubiquitylation. Cullin-based E3 complexes, that are well characterized E3s, are thought to regulate many cellular events. In this research, we try to clarify the function of one of Cu12-based E3s, ECV^<Fem1B>. Now we show that ECV^<Fem1B> is responsible for regulating the cellular level of Nek2, which functions as M-phase kinase, by targeting it for ubiquitylation and proteolysis. The elimination of Nek2 was impaired in Fem1B knockdown cells, resulting in abnormal accumulation of the protein. Coimmunoprecipitation analysis also revealed that Fem1B interacts with Nek2 in vivo. Overexpression of WT Nek2 promoted degradation of Nek2. Finally, the purified recombinant ECV^<Fem1B> complex mediated Nek2 ubiquitylation in vitro. These observations thus demonstrate that the ECV^<Fem1B> complex plays an important role in cell-cycle progression by determining the abundance of Nek2.
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Report
(3 results)
Research Products
(13 results)
