Research on Gene Expression Network via histone acetylation
| Project/Area Number |
12557018
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | THE INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) |
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Principal Investigator |
ISHII Shunsuke RIKEN, Molecular Gentics Laboratory, Chief Scientist, 分子遺伝学研究室, 主任研究員 (00124785)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2001: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Mutant mice / Transcription factor / Shn-2 / Transcriptional corepressor / Ski / Immune system / Cellular transformation / Development / 疾患モデル / 発がん / 形態異常 |
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| Research Abstract |
We have generated and analysed the mutant mice lacking transcription factor Shn-2. Shn-2 was originally identified by our group as a factor that binds to the NF-KB site, and a large protein of 270 kD with two metal-finger structures. Since Drosophila homologue of Shn acts in the dpp signaling pathway, vertebrate Shn is thought to act in the BMP/TGFβ/activin signaling pathway. Shn-2-deficient mice seems to be healthy, but have a defects of T-cell development. In the thimi of Shn-2 mutant mice, almost no single-positive T cells were observed. A series of analyses indicated that Shn-2 is essential for the positive selection of T ceils. These results suggest that the BMP/TGFβ/activin signaling pathway plays some role in the T cell development.
We have also analysed the physiological role of Ski by using the Ski-deficient mice. We treated the Ski heterozygous mutant mice with chemical carcinogen DMBA. No tumors were generated in wild-type mice, whereas significant numbers of Ski heterozygotes developed the tumors such as T- and B-cell lymphomas. Further, the mouse fibroblasts prepared from the Ski-deficient embryos had increased proliferative capacity compared to wild-type cells. In addition, the introduction of activated Ki-ras into Ski-deficient mouse embryonic fibroblasts resulted in neoplastic transformation. These finding demonsrrate that Ski acts as a tumor suppressor in some types of cells.
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Report
(3 results)
Research Products
(23 results)
