2002 Fiscal Year Final Research Report Summary
| Project/Area Number |
12307004
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OKAYAMA Hioto The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40111950)
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| Co-Investigator(Kenkyū-buntansha) |
JINNO Shigeki The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (10251224)
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| Project Period (FY) |
2000 – 2002
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| Keywords | fission yeast / sister chromatid cohesion / G2-M transition control / checkpoint control / Cdc2 / Weel / Cdc25 |
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| Research Abstract |
Using fission yeast and cultured mammalian cells, we investigated the four key regulatory systems controlling the cell cyclle and differentiation : 1) the mechanism that enables the anchorage-independent cell cycle start, the most fundamental phenotype of cancer cells ; 2) the mechanism that controls cell competence to proliferate under growth-suppressive conditions : 3) the mechanism by which sister chromatid cohesion is formed and maintained : 4) the function of mammalian homolog of Rcd1a factor initially identified to be essential for nitrogen starvation-induced differentiation of fission yeast. We made the following critical findings. 1) Mammalian Cdc6, a key factor for activating origins of replication, requires anchorage for its expression, and enforced expression of Cdk6 and activation of Cdk4/6 and Cdk2 are sufficient for inducing the anchorage-independent S phase onset. 2) The Cdk6-cyclin D3 complex can evade inhibition by GKIs, thereby uniquely enhance cell's proliferative competence under growth-suppressive conditions and consequently sensitize cells to chemically and physically induced malignant transformation. 3) Sister chromatid cohesion in fission yeast are formed and maintained by an zipper-like mechanism involving newly identified Eso1 and Pdf5. 4) The mammalian homolog of fission yeast Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation and organ development.
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[Publications] Masuda,M., Nagai,Y., Oshima,N., Tanaka,K., Murakami,H., Igarashi,H., Okayama,H.: "Genetic Studies with the Fission Yeast Schizosaccharomyces pombe Suggest Involvement of Wee1, Ppa2, and Rad24 in Induction of Cell Cycle Arrest by Human Immunodeficiency Virus Type 1 Vpr"J.Virol.. 74. 2636-2646 (2000)
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[Publications] Tanaka,K., Yonekawa,T., Kawasaki,Y., Kai,M., Furuya,K., Iwasaki,M., Murakami,H., Yanagida,M., Okayama,H.: "fission yeast Eso1p Is Required for Establishing Sister Chromatid Cohesion during S Phase"Molecular And Cellular Biology. 20-10. 3459-3469 (2000)
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[Publications] Notomi,T., Okayama,H., Masubuchi,H., Yonekawa,T., Watanebe,K., Amino,N., Hase,T.: "Loop-mediated isothermal amplification of DNA"Nuc.Acids Res.. 28. e63 (2000)
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[Publications] Nakanishi,M., Ando,H., Watanabe,N., Kitamura,K., Ito,K., Okayama,H., Miyamoto,T., Aguli,T., Sasaki,M.: "Idntification and characterization of human Wee1B, a new member of the Wee1 family of Cdk-inhibitofy kinases"Genes to Cells. 5. 839-847 (2000)
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[Publications] Nakamura,E., Isobe,H., Tomita,N., Sawamura,M., Jinno,S., Okayama,H.: "Functionallized Fulleren as an Artificial Vector for Transfection"Angew.Chem.Int.Ed.. 39-23. 4254-4257 (2000)
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[Publications] Tsukahara,K., Watanabe,T., Hata-Sugi,N., Yoshimatsu,K., Okayama,H., Nagasu,T.: "Anticancer agent e7070 inhibits amino acid and uracil transport in fission yeast"Mol.Pharmacol.. 60. 1254-1259 (2001)
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[Publications] Tanaka,H., Ryu,G.-H., Seo,Y.-S., Tanaka,K., Okayama,H., Macneill,S.A., Yuasa,Y.: "The fission yeast pfh1^+ gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase"Nucleic Acids Research. 30-22. 4728-4739 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Hiro,N., Ito,T., Yamamoto,H., Ochiya,T., Jinno,S., Okayama,H.: "Mammalian Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation"The EMBO Journal. 21-19. 5235-5244 (2002)
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