Signal transduction by centrosome-associated protein kinases
Project/Area Number |
24590396
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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 |
Pathological medical chemistry
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Research Institution | Aichi Cancer Center Research Institute |
Principal Investigator |
GOTO Hidemasa 愛知県がんセンター(研究所), 腫瘍医化学部, 室長 (20393126)
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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 |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 分裂期 / キナーゼ / Plk1 / 14-3-3 / PI3キナーゼ / Akt / 中心体 / 14-3-3ガンマ |
Outline of Final Research Achievements |
Polo-like kinase 1 (Plk1) controls multiple aspects of mitosis. Here, we identified Ser99 on Plk1 as a novel mitosis-specific phosphorylation site. Plk1-Ser99 phosphorylation creates a docking site for 14-3-3gamma and this interaction stimulates the catalytic activity of Plk1. 14-3-3gamma knockdown or replacement of wild-type Plk1 by a Ser99-phospho-blocking mutant leads to a prometaphase/metaphase-like arrest due to the activation of the spindle assembly checkpoint. Inhibition of PI3K and Akt significantly reduces the level of Plk1-Ser99 phosphorylation and delays metaphase to anaphase transition. Mitotic Plk1 activity is regulated by Plk1 binding to 14-3-3gamma following Plk1-Ser99 phosphorylation downstream of the PI3K-Akt signalling pathway. This novel Plk1 activation pathway controls proper progression from metaphase to anaphase. Our study paves the way for future studies elucidating the relationship between PI3K-Akt pathway and Plk1 in carcinogenesis.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Plk1 Phosphorylates CLIP-170 and Regulates Its Binding to Microtubules for Chromosome Alignment2014
Author(s)
Kaneko M., Matsuzawa K., Matsui T., Akita H., Sugiyama I., Ishidate F., Nakano A., Takashima S., Goto H., Inagaki M., Kaibuchi K., and Watanabe T.
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Journal Title
Cell Structure and Function
Volume: 39
Issue: 1
Pages: 45-59
DOI
NAID
ISSN
0386-7196, 1347-3700
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cyclin A/Cdk2 regulates Cdh1 and claspin during late S/G2 phase of the cell cycle.2014
Author(s)
Oakes, V., Wang, W., Harrington, B., Lee, W.J., Beamish, H., Chia, K.M., Pinder, A., Goto, H., Inagaki, M., Pavey, S., and Gabrielli, B.
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Journal Title
Cell Cycle
Volume: 13
Issue: 20
Pages: 3302-3311
DOI
Related Report
Peer Reviewed
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[Journal Article] PI 3-kinase-dependent phosphorylation of Plk1-Ser99 promotes association with 14-3-3γ and is required for metaphase-anaphase transition2013
Author(s)
Kasahara, K., Goto, H., Izawa, I., Kiyono, T., Watanabe, N., Elowe, S., Nigg, E.A. and Inagaki, M.
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Journal Title
Nat. Commun.
Volume: 4
Issue: 1
Pages: 1882-1882
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation2012
Author(s)
Li, P., Goto, H., Kasahara, K., Matsuyama, M., Wang, Z., Yatabe, Y., Kiyono, T., Inagaki, M.
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Journal Title
Mol. Biol. Cell
Volume: 23
Issue: 8
Pages: 1582-1592
DOI
Related Report
Peer Reviewed
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[Presentation] Screening of novel Aurora-A-associated proteins
Author(s)
Goto H., Era S., Li P., Kasahara K., Inoko A., Izawa I., Mochizuki H., Togashi T., Kawamura Y., Kawakami Y., Goshima N., Kiyono T., and Inagaki M.
Organizer
第72回日本癌学会総会
Place of Presentation
パシフィコ横浜(横浜市)
Related Report
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