Regulatory mechanisms involved in SRF-MKL1/2 complex in epithelial tumors
| Project/Area Number |
17K07154
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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 | Chiba University |
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Principal Investigator |
Iba Hideo 千葉大学, 真菌医学研究センター, 特任教授 (60111449)
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| Co-Investigator(Kenkyū-buntansha) |
原口 健 千葉大学, 真菌医学研究センター, 特任准教授 (10549455)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | SWI/SNF複合体 / Brm / MKL1/2 / SRF / SWI/SNFクロマチン構造因子 / 核内アクチン / 上皮細胞 / アクチン / SWI/SNF 複合体 / 上皮がん細胞 |
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| Outline of Final Research Achievements |
We showed that in human epithelial tumors, expression the catalytic subunit of SWI/SNF complex, Brm is negatively corelated with the expression of target genes of transcription factor, SRF and that Brm expression negatively regulates SRF function. By examining this molecular mechanism, we have found that 1) MKL1/2, important cofactors of SRF, were regulated by its subcellular localization; in Brm competent cells, MKL1/2 is retained in cellular cytoplasm. 2) Expression of one member of importin family genes was shown to be Brm-dependent, but this importin protein has no effects on the subcellular localization of MKL1/2.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの上皮がん細胞では、SWI/SNF複合体の触媒サブユニット Brmの発現の有無によって細胞内の多くの遺伝子群の制御ネットワークが決定的に違う２群に分けられることを見出してきた。その分子機構を理解することは、両群ごとに適切な治療法を開発する上で重要であると考えられることから、本研究では、MKL1/2の機能がBrmにより負に制御することに注目した。その結果MKL1/2の細胞内局在がBrmの発現により大きく影響を受けていることが判明した。現在その機構は解明には至っていない。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Tumor suppression via inhibition of SWI/SNF complex-dependent NF-κB activation.2017
Author(s)
1.Kobayashi, K*., Hiramatsu, H*., Nakamura, S., Kobayashi, K., Haraguchi, T. and Iba, H. (* equally contributed)
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Journal Title
Scientific Reports,
Volume: 7
Issue: 1
Pages: 11772-11772
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MiR-199a inhibits secondary envelopment of Herpes Simplex Virus-1through the downregulation of Cdc42-specific GTPase activating protein localized in Golgi apparatus.2017
Author(s)
2.Kobayashi, K., Suemasa, F., Sagara, H., Nakamura, S., Ino, Y., Kobayashi, K., Hiramatsu, H., Haraguchi, T., Kurokawa, K., Todo, T., Nakano, A., and Iba, H.
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Journal Title
Scientific Reports,
Volume: 7
Issue: 1
Pages: 6650-6650
DOI
Related Report
Peer Reviewed / Open Access
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