2005 Fiscal Year Final Research Report Summary
Regulation of cyclin-dependent kinases
| Project/Area Number |
13043015
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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 | Tokyo Institute of Technology |
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Principal Investigator |
KISHIMOTO Takeo Tokyo Institute of Technology, Grad. Sch. Biosci & Biotech., Professor, 大学院生命理工学研究科, 教授 (00124222)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Jun-ya Nara Institute of Scence and Technology, Grad. Sch. Biol. Sci., Professor, バイオサイエンス研究科, 教授 (00273839)
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| Project Period (FY) |
2001 – 2005
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| Keywords | cell cycle control / signal transduction / cell proliferation / Cdk-cyclin / Plkl / Akt / PKB / Jab 1 / Cdk inhibitor p27 |
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| Research Abstract |
We have investigated in vivo regulation and function of Cdk-cyclin complexes and their regulators.
1. Signalling pathways that lead to activation of cyclin B-Cdc2 have been studied at entry into various M- phases during meiotic and early embryonic cell cycles in starfish oocytes and eggs. Each signalling pathway is found to be composed of Akt/PKB-cyclin B-Cdc2 Plkl at the first meiosis, MAPK--Plkl-- cyclin B-Cdc2 at the second meiosis, and cyclin A-Cdc2-Plkl-cyclin B-Cdc2 at embryonic mitosis. In all of these pathways, a major target of Plkl is not Cdc25 but Mytl. These findings identify Akt/PKB with a novel role for a trigger kinase of M-phase, and also Plkl with novel upstream and downstream pathways.
2. Regulatory mechanisms have been studied how the activity of cyclin B-Cdc2 is maintained at elevated levels in metaphase-II arrest (CSF, cytostatic factor, arrest) of Xenopus oocytes. In contrast to the report by P. Jackson's group indicating that Emil is an essential component of CSF, we have demonstrated that in oocytes arresting at metaphase-II, Emil is undetectable and the APC/C is even functional, thus providing the study of CSF arrest with novel viewpoints.
3. Roles of Jabl for cell proliferation control have been studied in mammalian somatic cells. We have demonstrated : (1) Jabl promotes nuclear export and the resulting destruction of the Cdk inhibitor, p27, through binding to both CRM1 and p27 ; (2) Jabl is over expressed and activated in myelocytic leukemia, pancreatic cancer and lung cancer, accompanied with unusal destruction of p27 and accerelation of malignancy ; (3) Jabl-knockout mice are embryonic lethal, accompanied with over expression of cyclin E, p53, and p27 which might cause inhibition of cell proliferation and activation of apoptosis ; (4) Jabl transgenic mice suffer leukemia, possibly due to perturbed expression and intracellular localization of p27 andp16.
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Research Products
(41 results)
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[Journal Article] The Jabl/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression.2005
Author(s)
Tomoda, K, Kato, J.Y, Tatsumi, E, Takahashi, T, Matsuo, Y, Yoneda-Kato, N.
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Journal Title
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Small Jab1-containing subcomplex is regulated in an anchorage-and cell cycle-dependent manner, which is abrogated by ras transformation.2005
Author(s)
Fukumoto, A, Tomoda, K, Kubota, M, Kato, J.Y, Yoneda-Kato, N.
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Journal Title
FEBS Lett 579
Pages: 1047-1054
Description
「研究成果報告書概要(和文)」より
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[Journal Article] The Jabl/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression.2005
Author(s)
Tomoda, K., Kato, J.Y., Tatsumi, E., Takahashi, T., Matsuo, Y., Yoneda-Kato, N.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Small Jab 1-containing subcomplex is regulated in an anchorage-and cell cycle-dependent manner, which is abrogated by ras transformation.2005
Author(s)
Fukumoto, A., Tomoda, K., Kubota, M., Kato, J.Y., Yoneda-Kato, N.
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Journal Title
FEBS Lett. 579
Pages: 1047-1054
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] PDK1 is required for the hormonal signalling pathway leading to meiotic resumption in staefish oocytes.2004
Author(s)
Hiraoka, D, Hori-Oshima, S, Fukuhara, T, Tachibana, K, Okumura, E, Kishimoto, T.
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Journal Title
Dev.Biol. 276
Pages: 330-336
Description
「研究成果報告書概要(和文)」より
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[Journal Article] PDK1 is required for the hormonal signalling pathway leading to meiotic resumption in starfish oocytes.2004
Author(s)
Hiraoka, D., Hori-Oshima, S., Fukuhara, T., Tachibana, K, Okumura, E., Kishimoto, T.
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Journal Title
Dev. Biol. 276
Pages: 330-336
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Distinct regulators for Plk1 activation in starfish meiotic and early embryonic cycles.2003
Author(s)
Okano-Uchida, T, Okumura, E, Iwashita, M, Yoshida, H, Tachibana, K, Kishimoto, T
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Journal Title
EMBO J. 22
Pages: 5633-5642
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Distinct regulators for Plk1 activation in starfish meiotic and early embryonic cycles.2003
Author(s)
Okano-Uchida, T., Okumura, E., Iwashita, M., Yoshida, H., Tachibana, K., Kishimoto, T.
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Journal Title
EMBOJ. 22
Pages: 5633-5642
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Akt inhibits Mytl in the signalling pathway that leads to meiotic G2/M-phase teansition.2002
Author(s)
Okumura, E, Fukuhara, T, Yoshida, H, Hanada, S, Kozutsumi, R, Mori, M, Tachibana, K, Kishimoto
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Journal Title
Nature Cell Biol. 4
Pages: 1111-116
Description
「研究成果報告書概要(和文)」より
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[Journal Article] The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex.2002
Author(s)
Tomoda, K, Kubota, Y, Arata, Y, Mori, S, Maeda, M, Tanaka, T, Yoshida, M, Yoneda-Kato, N, Kato, J-Y.
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Journal Title
J.Biol.Chem. 227
Pages: 2302-2310
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Akt inhibits Mytl in the signalling pathway that leads to meiotic G2/M- phase transition.2002
Author(s)
Okumura, E., Fukuhara, T., Yoshida, H., Hanada, S., Kozutsumi, R., Mori, M., Tachibana, K., Kishimoto, T.
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Journal Title
Nature Cell Biol. 4
Pages: 111-116
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The cytoplasmic shuttling and subsequent degradation of p27Kipl mediated by Jabl/CSN5 and the COP9 signalosome complex.2002
Author(s)
Tomoda, K., Kubota, Y., Arata, Y., Mori, S., Maeda, M., Tanaka, T., Yoshida, M., Yoneda-Kato, N., Kato, J-Y.
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Journal Title
J. Biol. Chem. 277
Pages: 2302-2310
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Direct binding of the signal-transducing adaptor Grb2 facilitates downregulation of the cyclin-dependent-kinase inhibitor p27Kipl.2001
Author(s)
Sugiyama, Y., Tomoda, K., Tanaka, T., Arata, Y., Yoneda-Kato, N., Kato, J-Y
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Journal Title
J. Biol. Chem. 276
Pages: 12084-12090
Description
「研究成果報告書概要(欧文)」より
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[Book] 発生における細胞増殖制御2004
Author(s)
竹内隆, 岸本健雄(編集)
Total Pages
198
Publisher
シュリンプガーフェアラーク東京
Description
「研究成果報告書概要(和文)」より
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[Book] Tumorsuppressing Viruses, Genes and Drugs : Innovative Cancer Therapy Approaches (Maruta H ed.)2001
Author(s)
Kato, J-Y, Tomoda, K, Arata, Y, Tanaka, T, Yoneda-Kato, N.
Total Pages
200
Publisher
Academic Press ( San Diego )
Description
「研究成果報告書概要(和文)」より
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