| Budget Amount *help |
¥88,010,000 (Direct Cost: ¥67,700,000、Indirect Cost: ¥20,310,000)
Fiscal Year 2015: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2014: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2013: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2012: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2011: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
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| Outline of Final Research Achievements |
NRF2 is a master transcriptional activator playing a critical role in the defense mechanism against oxidative insults. NRF2 activates many cytoprotective genes in response to reactive oxygen species (ROS). Under unstressed conditions, NRF2 is constantly ubiquitinated by KEAP1 and degraded in the proteasome. During exposure to ROS, KEAP1 is inactivated, and NRF2 is stabilized. Consequently, NRF2 activates transcription, conferring resistance against xenobiotic and oxidative stress. While NRF2 activation is beneficial to our health, NRF2 is responsible for the malignant progression of various human cancers. We found that NRF2 not only enhances survival of cancers by activating cytoprotective genes but also redirects glucose and glutamine into anabolic pathways by activating metabolic genes, which are advantageous for cancer proliferation. Enhanced activity of PI3K-AKT signaling enables NRF2 to induce the metabolic genes and modulate metabolism.
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