Basic and Applied Research on tie Roles of Ca^<2+>-Signal-mediated Cell-Cycle Regulation in Budding Yeast.
| Project/Area Number |
17208009
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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 |
Applied biochemistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
MIYAKAWA Tokichi Hiroshima University, Graduate School of Advanced Sciences of Matter, Professor (10116676)
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| Co-Investigator(Kenkyū-buntansha) |
KADOTA Shigetoshi Toyama Univ., Wakanyaku Inst, Professor (90115163)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2007: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2006: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2005: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
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| Keywords | Saccharomvces cerevisiae / Ca^<2+> sienal transduction / Calcineurin / Cell cycle regulation / S-adenosvl methionine / HOG pathway / Cell cycle checknoint / Protein kinase C / Ca2+シグナル / 細胞周期 / ラディシコール / YAP1 |
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| Research Abstract |
Analyses of cell-cycle regulation and investigation of its physiological role For understanding detailed mechanism for the Ca^<2+>-signal mediated cell-cycle regulation in yeast, we isolated mutants (designated scz) defective in this process and performed molecular genetic analyses of the mutants.
(1) By the analysis of scz6 mutation, we found that the phenotype is caused by a mutation of PKC1 gene. We further demonstrated that C-kinase and A-kinase antagonistically regulates Cln2, and thereby regulate cell growth and polarized bud growth, suggesting a crosstalk between A-kinase and C-kinase pathways.
(2) By the analysis of sczl3 mutation, we found a mutation of Alg9 which is involved in the protein N-glycosylation in the ER lumen is responsible for suppression of the Ca^<2+> phenotype. We found that N-glycosylation of proteins is important for the maintenance of Swel and Cln2 levels.
We also developed a procedure to detect bioactive compounds which inhibit Ca^<2+>-signal mediated cell-cycle regulation and screened for active substances from various sources. We investigated action mechanisms of two small-molecule compounds found by the screening.
(1) Radicicol, inhibitor of Hsp90, inhibits Ca^<2+>-signal mediated cell-cycle regulation by destabilizing Swel, inhibitory Idnase of Cdc28/Clb.
(2) By molecular genetic analysis of the mutants resistant to NKH-7, we identified Tubl α-tubulin as target of this compound. Based on its physiological effect and mutation site of Tub I, we suggested that NKH-7 destabilizes microtubules by binding to Tubl α-tubulin.
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Report
(4 results)
Research Products
(71 results)
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[Journal Article] Identification of Tubl a-Tubulin as a Potential Target for NKH-7, a cytotoxic 1-Naphthol Derivative Compound2008
Author(s)
R., Chanklan, M., Mizunuma, N., Kongkathip, K., Hasitapan, B., Kongkathip, T., Miyakawa
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Journal Title
Biosel Biotechnol Biochem 72(in Press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Identification of Tupl and Cyc8 mutations defective in the responses to osmotic stress2008
Author(s)
Y., Kobayashi, T., Thai, M., Mizunuma, I., Okada, A., Shitamukai, D., Hirata, T., Miyakawa
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Journal Title
Biochem. Biophys. Res. Commun 368
Pages: 50-55
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Inhibition of Ca^<2+>-signal-sependent growth regulation by eadicicol in budding yeast2008
Author(s)
R., Chanklan, E., Aihara, S., Koga, H., Takahashi, M., Mizunuma, T., Miyakawa
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Journal Title
Biosci, Biotechnol. Biochem 72
Pages: 132-138
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] YCM1008A, a novel Ca^<2+>-signaling inhibitor, produced by Fusarium sp.YCM10082007
Author(s)
F., Koizumi, N., Fukumitsu, J., Zhao, R., Chanklan, T., Miyakawa, S., Kawahara, S., Iwamoto, M., Suzuki, S., Kakita, E.S., Rahayu, S., Hosokawa, K., Tatsuta, M., Ichimura
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Journal Title
J Antibiotics 60
Pages: 455-458
Description
「研究成果報告書概要(欧文)」より
Related Report
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