|Budget Amount *help
¥195,780,000 (Direct Cost: ¥150,600,000、Indirect Cost: ¥45,180,000)
Fiscal Year 2016: ¥37,440,000 (Direct Cost: ¥28,800,000、Indirect Cost: ¥8,640,000)
Fiscal Year 2015: ¥37,440,000 (Direct Cost: ¥28,800,000、Indirect Cost: ¥8,640,000)
Fiscal Year 2014: ¥37,700,000 (Direct Cost: ¥29,000,000、Indirect Cost: ¥8,700,000)
Fiscal Year 2013: ¥37,440,000 (Direct Cost: ¥28,800,000、Indirect Cost: ¥8,640,000)
Fiscal Year 2012: ¥45,760,000 (Direct Cost: ¥35,200,000、Indirect Cost: ¥10,560,000)
|Outline of Final Research Achievements
We found that histone H2A Thr 120 is phosphorylated in human cancer cell lines and proved that H2A Thr 120 phosphorylation is catalyzed by hVRK1. By knocking down VRK1, cyclin D1 was found to be down-regulated by loss of H2A Thr120 phosphorylation and increased H2A Lys119 ubiquitylation of its promoter region resulted in impaired cell growth. In vivo, we identified that histone H2A is hyper-phosphorylated with up-regulated cyclin D1 in human gastrointestinal tract cancer tissues. In vitro, mutated H2A Thr 120 Asp that mimics phosphorylation transformed NIH3T3 cells. This suggested that histone H2A Thr 120 hyper-phosphorylation by hVRK1 causes inappropriate gene expression including up-regulated cyclin D1, resulting in carcinogenesis.
Ohkuma et al determined TFIIE structure using X-ray crystallography. They demonstrated that Mediator is functioning by activating essential genes using kinase module.