| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Outline of Final Research Achievements |
COP1 is an E3 ubiquitin ligase that is involved in tumorigenesis and metabolism. We aimed how cancer-initiating cells acquire a specific energy metabolic system essential for their proliferation in the process of cellular transformation by investigating the COP1’s activities linking both tumorigenesis and metabolism.
In this study, we newly identified COP1’s ligase-complexes and substrates for degradation, and depicted a presumable network map associated with COP1 activities. We are analyzing these factors using various cell culture systems and mouse models. In addition, we found that acute myeloid leukemia-associated MLF1 is an inhibitory factor of the ligase activity of the COP1-Trib1 complex. MLF1 directly interacts with COP1 and interferes with the formation of the COP1-Trib1 complex, thereby stabilizing C/EBPα protein and suppressing AML development in mice. Induction and stabilization of MLF1 expression have a potential as a novel strategy for cancer therapy.
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