| Project/Area Number |
25860244
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Saitama Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2013-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | ES細胞 / c-Myc / N-Myc / mouse ES / Max / Nanog / アポトーシス |
|---|
| Outline of Final Research Achievements |
In 2011, our lab reported that extinction of Max gene expression in ES cells provoke cell death. In this study, we found that Nanog is co-precipitated with N-Myc and c-Myc proteins in a Max protein independent manner. Next we performed the experiments with Myc-ER fusion protein and found that activation of Myc activities in ESCs provokes apoptosis like that observed with Max-null ES cells. Indeed, we found that c-Myc-ER stable transfectants of wild-type ESCs show extensive apoptotic phenotype by the addition of 4-hydroxytamoxifen. Based on these findings, we hypothesize that Myc proteins liberated from Max control in Max-KO ESCs attribute to apoptotic phenotype of Max-KO ESCs and Nanog can neutralize apoptosis-promoting activity of Myc proteins by interacting with them.
|
| Academic Significance and Societal Importance of the Research Achievements |
ES細胞においてMax欠損状態では、生物学的な機能を持たないであろうと考えられていたc-Mycが、アポトーシスを誘導するという思いもよらない現象を引き起こした。そこで申請者は、この現象を規定している分子メカニズムを解明する事は、c-Myc に関して全く新しい分子指標を見出すことに繋がるのではないかと考えている。そして、この研究は、c-Myc を標的としたES 細胞のアポトーシス誘導による、未分化状態の細胞を優先的に死滅させる創薬や排除させるシステムの構築の指針なると考えている。
|
