| Project/Area Number |
12307004
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | The University of Tokyo |
|---|
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)
|
|---|
| 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)
永田 昭久 東京大学, 大学院・医学系研究科, 講師 (50155933)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2002: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2001: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
|
|---|
| Keywords | fission yeast / sister chromatid cohesion / G2-M transition control / checkpoint control / Cdc2 / Weel / Cdc25 / G1 / 細胞周期開始 / DNA polymerase η |
|---|
| 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.
|
