| Project/Area Number |
12670107
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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 |
General medical chemistry
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| Research Institution | The University of Tokyo, |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Akihisa The University of Tokyo, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (50155933)
OKAYAMA Hiroto 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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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cell cycle / Anchorage / NRK / E2F / Cdk / Cdc6 / 足場非依存性増殖 / cdc6 / G1 / サイクリンD3 / 癌化 / cdk6 |
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| Research Abstract |
Fibroblasts need anchorage to extracellular matrix to transit from G1 to S phase, but no longer after oncogenic transformation. We report that Cdc6 protein essential for the activation of replication origins requires anchorage or oncogenic stimulation for its execution. Upon anchorage loss, Cdc6 expression is shut of both transcriptionally and post-transcriptionally in a rat fibroblast despite enforced activation of E2F-dependent promoters. However, stimulation of this cell with oncogenic growth factors suppresses this shutoff and concurrently activates Cdk2 and Cdk6/4, thereby overriding the anchorage requirement for the G1-S transition and consequently enabling cells to perform anchorage-independent S phase entry. Analysis with enforced expression of Cdc6 indicates that the G1 cyclin-dependent kinases and Cdc6 constitute major cell cycle targets for the restriction of the G1-S transition by anchorage loss.
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