2000 Fiscal Year Final Research Report Summary
Functional role of cyclin G for p53-dependent G2/M arrest by DNA
| Project/Area Number |
11671630
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NISHIDA Jun-ichi Medical Institute of Bioregulation Kyushu Univ.Research Associate, 生体防御医学研究所, 助手 (40264113)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Takao Medical Institute of Bioregulation Kyushu Univ.Research Associate, 生体防御医学研究所, 助手 (10304825)
KATO Kiyoko Medical Institute of Bioregulation Kyushu Univ.Assistant Professor, 生体防御医学研究所, 講師 (10253527)
KATO Hidenori Medical Institute of Bioregulation Kyushu Univ.Assistant Professor, 生体防御医学研究所, 講師 (60214392)
WAKE Norio Medical Institute of Bioregulation Kyushu Univ.Professor, 生体防御医学研究所, 教授 (50158606)
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| Project Period (FY) |
1999 – 2000
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| Keywords | P53 / cyclin G / DNA damage / NaB / acetylation / phosphorylation / G2 / M arrest / Sodium butylate |
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| Research Abstract |
To investigate the p53-dependent regulation of G2/M transition, we studied the association of cell cycle progression with expression of a p53 transcriptional target, cyclin G.DOX (doxorubicin) treatment produced an apparent increase in the number of cells in the G2/M fraction, which was abrogated by antisense oligoDNAs complementary to cyclin G mRNA, suggesting that cyclin Gacts as a negative regulator in G2/M transition. However, NaB (sodium butyrate), histon deacetylase inhibitor, arrested cells at G1.
P53 protein induced by DOX, that was phosphorylated at serine 15 and 392, upregulated p21 and cyclin G expression. In turn, p53 protein induced transiently by NaB was unphosphorylated and failed to up-regulate cyclin G expression. Both unphosphorylated and phosphorylated p53 proteins disclosed the enhanced transcriptional activities in response to DOX or NaB, and then, upregulated mdm2 mRNA expression. The difference in p53 phosphorylation in response to DOX or NaB possibly corresponds to the apparent G1 phase arrest in NaB treated cells, which contrast sharply with the dominant accumulation of DOX-treated cell in the G2/M phase fraction. DOX treatment resulted in the appearance of significant number of cells at sub G1 fraction. We produced cyclin G overexpressors that were susceptible to DOX treatment or serum deprivation, resulting in apoptosis. Markedly high expression levels of bax protein in exponentially growing cyclin G overexpressors contributed to this susceptibility. These results suggested a role for cyclin G in determining the destination of cells with DNA damage.
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