2017 Fiscal Year Final Research Report
Analysis of secretory pathway of 14-3-3sigma
| Project/Area Number |
15K15090
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 14-3-3 / 細胞外分泌 |
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| Outline of Final Research Achievements |
To elucidate the mechanism underlying the secretion of 14-3-3sigma, a series of experiments have been performed and the following results have been obtained.First, the analysis using various deletion mutants of 14-3-3sigma indicate that the N-terminal 82 amino acids region is important for its binding to CLSP. Treatment with brefendin results in the almost complete defect of 14-3-3sigma secretion. This result indicates that 14-3-3sigma is secreted via the so-called unconventional secretion pathway. Third, an secretion assay system has been established by which 14-3-3sigma, C-terminally tagged with Nanoluc, is overexpressed in cultured cells. Using this assay, the involvement of Grasp1 and Grasp2 in the secretion of 14-3-3sigma has been addressed. Until now, consistent results have not been obtained by the gain-of-function experiments or the loss-of-function experiments. Finally, no 14-3-3sigma-binding proteins other than CLSP have been identified.
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| Free Research Field |
薬理学
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