2015 Fiscal Year Final Research Report
Analysis of physiological function of the complex between the Down syndrome kinase DYRK1A and WDR68
| Project/Area Number |
25440046
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | DYRK1A / WDR68 / TRiC/CCT / WD40ドメイン / 分子シャペロン / タンパク質キナーゼ / シグナル伝達 / タンパク質間相互作用 |
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| Outline of Final Research Achievements |
WDR68 (Trp-Asp repeat protein 68) is an evolutionarily conserved WD40-repeat protein with multiple physiological functions. However, the biochemical basis and regulatory mechanism of WDR68 activity remain unknown. We have isolated and identified cellular WDR68-binding partners using a phospho-proteomic approach. Eight TCP1 subunits comprising the molecular chaperone TRiC/CCT were identified as major WDR68-binding proteins, and phosphorylation sites in WDR68 and TRiC/CCT were identified. Computer-aided structural analysis suggested that WDR68 forms a 7-bladed beta-propeller ring. Knockdown of cellular TRiC/CCT by siRNA caused an abnormal WDR68 structure and led to reduction of its DYRK1A-binding activity. Concomitantly, nuclear accumulation and cellular solubility of WDR68 was suppressed in TRiC/CCT-deficient cells. Altogether, our results demonstrate that the molecular chaperone TRiC/CCT is essential for correct protein folding, DYRK1A-binding, and nuclear accumulation of WDR68.
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| Free Research Field |
生化学・分子細胞生物学
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