2011 Fiscal Year Final Research Report
Control of mitotic apparatus by mitotic kinases
| Project Area | Cell Proliferation Control |
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| Project/Area Number |
19057008
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | 公益財団法人がん研究会・がん研究所 (2011)
Japanese Foundation For Cancer Research (2007-2010) |
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Principal Investigator |
HIROTA Toru 公益財団法人がん研究会・がん研究所, 実験病理部, 部長 (50421368)
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| Co-Investigator(Renkei-kenkyūsha) |
高垣 謙太郎 公益財団法人がん研究会がん研究所, 実験病理部, 博士研究員 (70419951)
内田 和彦 公益財団法人がん研究会がん研究所, 実験病理部, 博士研究員 (40380555)
進藤 軌久 公益財団法人がん研究会がん研究所, 実験病理部, 博士研究員 (00512253)
熊田 和貴 公益財団法人がん研究会がん研究所, 実験病理部, 博士研究員 (10370149)
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| Project Period (FY) |
2007 – 2011
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| Keywords | 細胞分裂 / 染色体 / 紡錘体 / 分裂期キナーゼ |
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| Research Abstract |
Cell division is a basis of cell proliferation, and thus must be under rigorous control. The research aimed to elucidate how mitotic apparatus are regulated by mitotic kinases including Cdk1, Aurora and Polo kinases. To study this, we first established a series of cell lines that stably express fluorescence labeled proteins in chromosomes, kinetochores and microtubules. We then set up a condition to study protein dynamics using the fluorescence recovery after photobleaching assay. Using these cell lines and technique, we obtained the following results: 1) Aurora B promotes the release of HP1α from chromosome arms in mitosis, but a small subset of HP1α become a part of the chromosomal passenger-complex (CPC) in a phosphorylation-dependent manner. HP1α was found out to be an essential component of the CPC to prevent mis-segregation of chromosomes. 2) Cdk1 targets a subunit of condensin II complex, CAP-D3 to initiate chromosome condensation as cells enter mitosis. A Cdk1-mediated phosphorylation of CAP-D3 induces recruitment of Plk1 and further propagation of phosphorylation widely on the complex, which promotes condensin II to assemble chromosomes. These findings highlight the distinct properties of Aurora and Polo kinases in regulating mitotic apparatus.
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[Journal Article] The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II.2011
Author(s)
Abe, S., Nagasaka, K., Hirayama, Y., Kozuka-Hata, H., Oyama, M., Aoyagi, Y., Obuse, C., and *Hirota, T.
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Journal Title
Genes Dev.
Volume: 25
Pages: 863-874
Peer Reviewed
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[Journal Article] CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment.2011
Author(s)
Ito, G., Kanno, S., Uchida, K.S.K, Chiba, S., Sugino, S., Watanabe, K., Mizuno, K., Yasui, A., Hirota, T., and *Tanaka, K.
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Journal Title
EMBO J.
Volume: 30
Pages: 130-144
Peer Reviewed
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[Journal Article] Differential control of Eg5 dependent centrosome separation by Plk1 and Cdk1.2011
Author(s)
Smith, E., Hegarat, N., Vesely, C., Roseboom, I., Streicher, H., Straatman, K., Flynn, H., Skehel, M., Hirota, T., Kuriyama, R., *Hochegger, H.
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Journal Title
EMBO J.
Volume: 30
Pages: 2233-2245
Peer Reviewed
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[Journal Article] Human POGZ modulates HP1 dissociation from mitotic chromosome arms through Aurora B activation.2010
Author(s)
Nozawa, R., Nagao, K., Masuda, H., Iwasaki, O., Hirota, T., Nozaki, N., Kimura, H., and *Obuse, C.
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Journal Title
Nat. Cell Biol.
Volume: 12
Pages: 719-727
Peer Reviewed
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[Journal Article] Requirement of ATM for Rapid p53 Phosphorylation at Ser46 without Ser/Thr-Gln Sequences.2010
Author(s)
Kodama, M., Otsubo, C., Hirota, T., Yokota, J., Enari, M., *Taya, Y.
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Journal Title
Mol. Cell. Biol.
Volume: 30
Pages: 1620-1633
Peer Reviewed
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[Journal Article] Kinetochore stretching inactivates the spindle assembly checkpoint.2009
Author(s)
Uchida, K.S.K., Takagaki, K., Kumada, K,, Noda, T., and *Hirota, T.
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Journal Title
J. Cell Biol.
Volume: 184
Pages: 383-390
Peer Reviewed
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[Journal Article] KIF1B-beta functions as a haploidinsufficient tumor suppressor gene mapped to chromosome 1p36.2 by inducing apoptotic cell death.2008
Author(s)
Munirajan, A.K., Ando, K., Mukai, A., Takahashi, M., Suenaga, Y., Ohira, M., Koda, T., Hirota, T., Ozaki, T., and *Nakagawara, A.
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Journal Title
J. Biol. Chem.
Volume: 283
Pages: 24426-24434
Peer Reviewed
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[Journal Article] Aurora-A overexpression induces cellular senescence in mammary gland hyperplastic tumors developed in p53-deficient mice.2008
Author(s)
Zhang, D., Shimizu, T., Araki, N., Hirota, T., Yoshie, M., Ogawa, K., Nakagata, N., Takeya, M., and *Saya. H.
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Journal Title
Oncogene
Volume: 27
Pages: 4305-4314
Peer Reviewed
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[Journal Article] The complete removal of cohesin from chromosome arms depends on separase.2007
Author(s)
Nakajima, M., Kumada, K., Hatakeyama, K., Noda, T., Peters, JM., and *Hirota, T.
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Journal Title
J. Cell Sci.
Volume: 120
Pages: 4188-4196
Peer Reviewed
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[Book] Immunocytochemistry for analyzing chromosomes., Chromosome Nanoscience and Technology2007
Author(s)
Hoshi, O., Hirota, T., Kimura, E., Komatsubara, N., Ushiki, T.
Total Pages
79-87
Publisher
CRC Press
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