Molecular bases for masking c-MYC dependent apoptosis common in embryonic stem cells and cancer cells
| Project/Area Number |
16H05143
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Saitama Medical University |
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Principal Investigator |
OKUDA AKIHIKO 埼玉医科大学, 医学部, 教授 (60201993)
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| Co-Investigator(Kenkyū-buntansha) |
平崎 正孝 埼玉医科大学, 医学部, 助教 (10522154)
依馬 正次 滋賀医科大学, 動物生命科学研究センター, 教授 (60359578)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Keywords | c-Myc / Max / 細胞増殖 / アポトーシス / c-MYC / MAX / がん細胞 / Myc / ES細胞 / MYC |
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| Outline of Final Research Achievements |
c-MYC, one of typical proto-oncogenes, is well-known to promote cell cycle progression by functioning as a transcription factor together with its obligated partner protein, MAX. c-MYC also bears apoptosis inducing activity as well. However, the molecular bases of c-MYC dependent apoptosis remains totally obscure. In this study, we focused on the latter activity of c-MYC. We firstly demonstrated that apoptosis induced by forced expression of c-MYC in mouse embryonic fibroblasts was significantly attenuated by simultaneous expression of NANOG. Secondly, physical interaction between c-MYC and NANOG was affected by relative amounts between c-MYC and MAX in which NANOG binds to c-MYC most strongly in the absence of MAX expression. Finally, we demonstrated that c-MYC has a potential to inhibit DNA replication, suggesting that apoptosis inducing activity of c-MYC reflects the result of replication stress induced by c-MYC.
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| Academic Significance and Societal Importance of the Research Achievements |
c-MYCは細胞増殖促進とアポトーシス誘導という諸刃の剣とも称すべき生物学的に相反する活性を有するが、c-MYCのアポトーシス誘導活性を規定している分子基盤については全くといってよいほどわかっていない。本研究ではその一部を明らかにしたが、その研究成果は、がん細胞の中では専ら細胞増殖促進が発揮されているc-MYCに対して、その細胞増殖促進活性を抑制し、その代わりにアポトーシス活性を発揮させるという今までにはない全く新しいがん治療薬の開発が期待される。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Identification of the coiled-coil domain as an essential Mbd3 element for preserving lineage commitment potential of embryonic stem cells2018
Author(s)
Masataka Hirasaki, Atsushi Ueda, Masamitsu N. Asaka, Kousuke Uranishi, Ayumu Suzuki, Masakazu Kohda, Yosuke Mizuno, Yasushi Okazaki, Masazumi Nishimoto, Jafar Sharif, Haruhiko Koseki, Akihiko Okuda
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Journal Title
Stem Cells
Volume: 印刷中
Issue: 9
Pages: 1355-1367
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Book] 実験医学2018
Author(s)
奥田晶彦
Total Pages
6
Publisher
羊土社
ISBN
9784758125055
Related Report
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