| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Outline of Final Research Achievements |
We identified IDH3, UCHL1, and LY6E as novel activators of HIF-1. IDH3 was found to induce tumor angiogenesis by stabilizing HIF-1A and upregulating HIF-1A TAD activity. UCHL1 was confirmed to promote distant tumor metastasis by deubiquitinating and stabilizing HIF-1A protein. LY6E was revealed to induce tumor angiogenesis by facilitating the transcriptional initiation of HIF-1A gene. The UCHL1-HIF-1 axis was found to induce radioresistance of cancer cells by increasing intracellular levels of an antioxidant, GSH, in a glucose-6-phosphate dehydrogenase-dependent pentose phosphate pathway (PPP)-dependent manner.
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