Molecular basis for the development of anti-tumor therapy by targeting HSF1.
| Project/Area Number |
15K06866
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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 therapeutics
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| Research Institution | Gunma University |
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Principal Investigator |
Oda Tsukasa 群馬大学, 生体調節研究所, 助教 (10323643)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMASHITA Takayuki 群馬大学, 生体調節研究所, 教授 (10166671)
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| Research Collaborator |
NAKAI Akira 山口大学, 大学院医学系研究科, 教授
FUJIMOTO Mitsuaki 山口大学, 大学院医学系研究科, 准教授
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 細胞老化 / HSF1 / p53 / MDM2 / DHRS2 |
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| Outline of Final Research Achievements |
Heat shock transcription factor 1 (HSF1) regulates the expression of a wide array of genes, control of the expression of heat shock proteins (HSPs) and cell growth. Although acute depletion of HSF1 induces cellular senescence, the underlying mechanisms are poorly understood. Here, we report that HSF1 depletion-induced senescence (HDIS) of human diploid fibroblasts (HDFs) was independent of HSP-mediated proteostasis but dependent on activation of the p53-p21 pathway, partly because of the increased expression of dehydrogenase/reductase 2 (DHRS2), a putative MDM2 inhibitor. We observed that HDIS occurred without decreased levels of major HSPs or increased proteotoxic stress in HDFs. Importantly, we found that activation of the p53-p21 pathway due to reduced MDM2-dependent p53 degradation was required for HDIS. Furthermore, we provide evidence that increased DHRS2 expression contributes to p53 stabilization and HDIS.
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Report
(4 results)
Research Products
(14 results)
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[Presentation] Apurinic/apyrimidinic endonuclease 1 is involved in the pathogenesis of acute myeloid leukemia2017
Author(s)
Yuya Kitamura, Takayuki Saitoh, Noriyuki Takahashi, Rumi Ino, Nanami Gotoh, Akihiko Yokohama, Tsukasa Oda, Takayuki Yamashita, Norifumi Tsukamoto, Hiroshi Handa, Hirokazu Murakami
Organizer
The 79th Annual Meeting of the Japanese Society of Hematology
Related Report
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[Presentation] Long non-coding RNA PVT1 and MYC are co-regulated by bromodomain protein BRD4 in multiple myeloma and associated with disease progression2017
Author(s)
Kazuki Homma, Tsukasa Oda, Yuki Murakami, Saki Watanabe, Rei Ishihara, Yuko Kuroda, Kei Kimura, Yuta Masuda, Tetsuhiro Kasamatsu, Nanami Gotoh, Kenichi Tahara, Nobuhiko Kobayashi, Hiroaki Shimizu, Takuma Ishizaki, Akihiko Yokohama, Norifumi Tsukamoto, Takayuki Saitoh, Hirokazu Murakami, Hiroshi Handa
Organizer
The American Society of Hematology
Related Report
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