| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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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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