2013 Fiscal Year Final Research Report
The study of cell-cycle dependent degradation of the Notch intracellular domain
| Project/Area Number |
24657139
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Cell biology
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| Research Institution | Kyushu University |
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Principal Investigator |
SAGATA Noriyuki 九州大学, 理学(系)研究科(研究院), 教授 (80142024)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | Notch / 細胞周期 / タンパク分解 / ユビキチン / 神経分化 |
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| Research Abstract |
The Notch signaling pathway plays crucial roles in important cell fate decisions. Activation of Notch signaling is triggered by extracellular interactions between Notch receptors and Delta-like ligands, and results in the release of the Notch intracellular domain (NICD) by proteolytic processing. NICD enters the nucleus, and acts as a transcriptional factor by forming a complex with several factors. NICD is an unstable protein and its degradation mediated by the SCF E3 ubiquitin ligase plays an important role in regulating the Notch signaling. In this study, we show that NICD is degraded from anaphase to G1 phase in the cell cycle, and that this cell-cycle dependent degradation is mediated by the SCF-Skp2 E3 ubiquitin ligase. In addition, we found that an F-box only protein interacts with NICD-Skp2 complex to regulate the cell-cycle dependent degradation of NICD. These results raise the possibility that the Notch signaling pathway might be regulated in cell-cycle dependent manner.
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