2010 Fiscal Year Final Research Report
Radiosensitization by targeting a novel MAP3K negative regulator STK38
| Project/Area Number |
20591491
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
ENOMOTO Atsushi The University of Tokyo, 大学院・医学系研究科, 助教 (20323602)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Keywords | 増感 / STK38 / リン酸化 / 酸化ストレス |
|---|
| 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.
|
-
-
[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
-
Journal Title
Cancer lett 293
Pages: 52-57
Peer Reviewed
-
[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
-
Journal Title
Cancer Res 70
Pages: 257-265
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
