Radiosensitization by targeting a novel MAP3K negative regulator STK38
| Project/Area Number |
20591491
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ENOMOTO Atsushi The University of Tokyo, 大学院・医学系研究科, 助教 (20323602)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 増感 / STK38 / リン酸化 / 酸化ストレス / GSK-3 / ストレス応答 / 細胞死 / ストレスシグナル / MAP3K |
|---|
| Research Abstract |
Serine-threonine kinase 38 (STK38) is a member of the protein kinase A (PKA)/PKG/PKC-like family (AGC). However, little is known about its functions or regulatory mechanisms. Among various environmental stresses, STK38 was specifically activated by X-irradiation or H_2O_2, and the phosphatidylinositol 3-kinase inhibitor wortmannin or AKT inhibitor IV suppressed this activation. STK38 was also activated by a constitutively active AKT1 or by GSK-3beta inhibitor VII. Co-immunoprecipitation analysis revealed that GSK-3 physically interacted with STK38 in cells. Overexpression of GSK-3beta inhibited the oxidative stress-stimulated STK38 activity. We identified GSK-3 as an STK38 kinase. GSK-3beta phosphorylated STK38 on residues S6 and T7 in vitro, largely depending on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. STK38's oxidative stress-stimulated activity was enhanced by alanine substitution at its priming sites and/or at S6 and T7, but was partially reduced by a phosphomimetic mutation at S6 or T7. Knockdown or overexpression of the phosphomimetic mutant of STK38 enhanced oxidative stress-induced cell death. Taken together, our results indicate that that GSK-3 inhibits STK38 full activation through phosphorylation, and suggest that the activation of STK38 is required for preventing cell death against oxidative stress.
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Edaravone, a known free radical scavenger, enhances X-ray-induced apoptosis at low concentrations.2010
Author(s)
N.Sasano, A.Enomoto, Y.Hosoi, Y.Katsumura, Y.Matsumoto, A.Morita, K.Shiraishi, K.Miyagawa, H.Igaki, K.Nakagawa
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Journal Title
Cancer lett 293
Pages: 52-57
Related Report
Peer Reviewed
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[Journal Article] Sodium orthovanadate is a bifunctional inhibitor of transcription -dependent and -independent p53-mediated apoptosis.2010
Author(s)
A.Morita, S.Yamamoto, B.Wang, K.Tanaka, N.Suzuki, S.Aoki, A.Ito, T.Nanao, S.Ohya, M.Yoshino, J.Zhu, A.Enomoto, Y.Matsumoto, O.Funatsu, Y Hosoi, M.Ikekita
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Journal Title
Cancer Res 70
Pages: 257-265
NAID
Related Report
Peer Reviewed
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[Book] 医用放射化学
Author(s)
福士政広(共著)
Publisher
医療科学社(印刷中(掲載確定))
Related Report
