2015 Fiscal Year Final Research Report
Elucidation of the molecular mechanism involved in dysregulation of PTEN phosphorylation and its physiological role in cancers
| Project/Area Number |
25430113
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | NDRG2 / PTEN / リン酸化修飾 / ATL |
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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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| Free Research Field |
腫瘍生化学
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