Study on the molecular mechanism of genome instability in the cells with overexpression of PPM1D
| Project/Area Number |
24570146
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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 |
Functional biochemistry
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| Research Institution | Niigata University (2013-2014)
Hokkaido University (2012) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SAKAGUCHI Kazuyasu 北海道大学, 大学院理学研究院, 教授 (00315053)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ホスファターゼ / 酵素 / 染色体不安定性 / がん |
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| Outline of Final Research Achievements |
PPM1D was originally identified as a p53-inducible Ser/Thr phosphatase. We have found that PPM1D-overexpressed cells often show “DNA bridge” which is one of chromosome segregation errors, however the mechanism remains obscure.
In this study, we showed that PPM1D overexpression induced DNA bridge in p53-independent manner. Co-immunoprecipitation analysis showed that PPM1D interacts with nuclear phosphorylated protein, TOP2A. Overexpressed PPM1D co-localized with endogenous TOP2A not only in the nucleus but also on the DNA bridge during anaphase in mitosis. Decatenation assay exhibited that overexpressed PPM1D suppresses the TOP2A activity. The phosphorylation analysis of TOP2A exhibited that overexpressed PPM1D induced the elevation of low level of phosphorylated-TOP2A. These data suggested that overexpression of PPM1D induces genome instability through the inhibition of TOP2A activity by the regulation of TOP2A phosphorylation level.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Synthesis of yellow and red fluorescent 1,3a,6a-triazapentalenes and the theoretical investigation of their optical properties2015
Author(s)
Kosuke Namba, Ayumi Osawa, Akira Nakayama, Akane Mera, Fumi Tano, Yoshiro Chuman, Eri Sakuda, Tetsuya Taketsugu, Kazuyasu Sakaguchi, Noboru Kitamura, Keiji Tanino
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Journal Title
Chemical Science
Volume: 6
Issue: 2
Pages: 1083-1093
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Secreted Frizzled-Related Protein Potentiation versus Inhibition of Wnt3a/β-catenin Signaling2014
Author(s)
1. Xaviera, C.P., Melikova, M., Chuman, Y., Üren, A., Baljinnyam, B., Rubin, J.S.
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Journal Title
Cell. Signal
Volume: 26
Issue: 1
Pages: 94-101
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Formation of Functionalized Nanowires by Control of Self-Assembly Using Multiple Modified Amyloid Peptides2013
Author(s)
Sakai H, Watanabe K, Asanomi Y, Kobayashi Y, Chuman Y, Shi L, Masuda T, Wyttenbach T, Bowers MT, Uosaki K, Sakaguchi K
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Journal Title
Advanced Functional Materials
Volume: 23
Issue: 39
Pages: 4881-4887
DOI
Related Report
Peer Reviewed
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