Interplay between a circadian clock regulator, PER2, and HIF-1
Project/Area Number |
26461886
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Radiation science
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Research Institution | Kyoto University |
Principal Investigator |
Morinibu Akiyo 京都大学, 放射線生物研究センター, 研究員 (20722648)
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Co-Investigator(Kenkyū-buntansha) |
吉村 通央 京都大学, 医学研究科, 助教 (40597936)
原田 浩 京都大学, 放射線生物研究センター, 教授 (80362531)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | がん / 低酸素 / 概日リズム / HIF-1 / 糖代謝 |
Outline of Final Research Achievements |
HIF-1 is a transcription factor functioning in cellular responses to hypoxia. Recent studies have suggested that HIF-1 activity is upregulated by a circadian clock gene, PER2. Here, we analyzed its underlying mechanism in detail. Co-immunoprecipitation experiments and ChIP assay revealed that PER2 interacted with HIF-1α and facilitated the recruitment of HIF-1α to its enhancer, HRE. The PER2-mediated activation of HIF-1 was observed only when HIF-1α N803 was unhydroxylated. However, the extent of PER2-HIF-1α interaction was equivalent regardless of the N803 hydroxylation status. Taken together, these results suggest that, with the help of an unknown sensor molecule for the N803 hydroxylation status, PER2 functions as an effector molecule for the recruitment of HIF-1 to promoter regions of its downstream genes. Our findings provide a novel regulatory step in the activation of HIF-1, which can be targeted to develop therapeutic strategies against HIF-1-related diseases, e.g. cancers.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Aberrant IDH3alpha expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis2015
Author(s)
Zeng L, Morinibu A, Kobayashi M, Zhu Y, Wang X, Goto Y, Yeom CJ, Zhao T,Hirota K, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hammond EM, Hiraoka M, Harada H.
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Journal Title
Oncogene
Volume: epub
Pages: 4758-4766
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on ​HIF-1α.2015
Author(s)
Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
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Journal Title
Nature communication
Volume: 6
Pages: 1-10
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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