| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
NDRG2 is frequently down-regulated in various type of cancers including ATL. NDRG2 regulates PI3K/AKT pathway by dephosphorylation of PTEN via recruitment of PP2A. In this study, we found that NDRG2 acts as a novel negative feedback regulator in the PI3K/AKT pathway. PI3K-activated SGK1 phosphorylates NDRG2-Ser332 to promote PP2A binding to NDRG2 and dephosphorylation of PTEN, which plays a crucial role in the control of level of AKT activation. In addition, we identified Ser/Thr kinase SCYL2 as a novel PTEN interacting protein that functions in phosphorylation of PTEN-STT. SCYL2 expression is up-regulated in ATL cells and is essential for the enhanced PTEN-STT phosphorylation. As a potential physiological relevance of NDRG2 down-regulation, we demonstrated that NDRG2 inactivation renders ATL cells resistant to growth inhibition under hypoxic condition through sustained AKT activation, which may play a role in ATL development and progression.
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