2005 Fiscal Year Final Research Report Summary
| Project/Area Number |
13043002
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | University of Tsukuba |
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Principal Investigator |
TOYOSHIMA Hideo University of Tsulcuba, Graduate School of Comprehensive Human Sciences, Lecturer, 大学院人間総合科学研究科, 講師 (20197966)
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| Co-Investigator(Kenkyū-buntansha) |
OHTSUBO Motoaki Hiroshima University, RIRBM, Research Associate, 原爆放射線医科学研究所, 助手 (10211799)
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| Project Period (FY) |
2001 – 2005
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| Keywords | CDKinhibitor / cell cycle / cyclin / cyclindependent kinase (cdk) / SREBP / cell differentiation / DNA replication / lipid metabolism |
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| Research Abstract |
Search for interacting proteins of p57CDK inhibitor revealed that p57 binds to LIM kinase-1, a key regulator of actin filament under G-protein signaling cascade. p57 turned out to control not only cell cycle but also cytoskeleton and cell differentiation through binding to LIM kinase-1 by translocating the protein from cytoplasms to nucleus. Transgenic mice expressing SREBP (sterol regulatory element binding protein), a master regulator of lipid metabolism, specifically in liver turned out to show massive liver enlargement. Further analysis showed that SREBP directly induces the transcriptional expression of p21CDK inhibitor, thus may controls not only lipid metabolism but also cell cycle and cell proliferation.
Human diploid fibroblasts (HDF) rarely, if ever, undergo spontaneous transformation to an immortalized cell type. We observed the immortalization of an HDF cell line following transduction with cyclin A2 or cdkl genes via retroviral vectors. Cytogenetic studies revealed that the immortal lines share common chromosomal aberrations. FISH studies revealed frequent loss or translocations of one copy of tumor suppressor genes, relative to the parental cells. Deregulated expression of cyclin A2 or cdkl appeared to enhance the immortalization of the HDF through the induction of chromosomal aberrations.
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