1997 Fiscal Year Final Research Report Summary
Mechanism of Action and Clinical Application of the Type beta Transforming Growth Factor
| Project/Area Number |
07557334
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Japanese Foundation for Cancer Research |
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Principal Investigator |
MIYAZONO Kohei The Cancer Institute, Department of Biochemistry, Chief, 癌研究所生化学部, 部長 (90209908)
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| Co-Investigator(Kenkyū-buntansha) |
HANAI Jun-ichi The Cancer Institute, Dept., Biochemistry, Researcher, 癌研究所生化学部, 研究員 (70261964)
KATO Mitsuyasu The Cancer Institute, Dept., Biochemistry, Researcher, 癌研究所生化学部, 研究員 (20194855)
KAWABATA Masahiro The Cancer Institute, Dept., Biochemistry, Associate Member, 癌研究所生化学部, 主任研究員 (60224838)
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| Project Period (FY) |
1995 – 1997
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| Keywords | TGF-beta / receptor / tumor suppressor gene / signal transduction / growth inhibition / Smad / serine / threonine kinase / apoptosis |
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| Research Abstract |
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates the growth and differentiation of various cell types. TGF-beta binds to type I and type II serine/threonine kinase receptors, and activates Smad family of intracellular proteins.
(1) We investigated the expression of TGF-beta receptors in various carcinoma cell lines. In retinoblastoma cell lines, expression of the TGF-beta type II receptor is downregulated, but it was induced after cellular differentiation. Abnormality in the type I receptors was also suggested, but Smad proteins appeared to be intact.
(2) By yeast two-hybrid system using type I receptors as baits, we have obtained various proteins. Among those, we obtained Drosophila inhibitor of apoptosis-1 (DIAP-1), which appears to be involved in the signal transduction of TGF-beta family members.
(3) We have determined the exon-intron structure of Smad2. We also identified that there is an alternative spliced variant of Smad2, which lacks exon3. Such a variant of Smad2 has higher transcriptional activity than Smad2 with the exon3.
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[Publications] Okadome, T., Oeda, E., Saitoh, M., Ichijo, H., Moses, H.L., Miyazono, K., and Kawabata, M.: "Characterization of the interaction of FKBP12 with the transforming growth factor-b type I receptor in vivo" J.Biol.Chem. 271 (36). 21687-21690 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Persson, U., Souchelnytskyi, S., Franzen, P.Miyazono, K., ten Dijke, P., and Heldin, C.-H.: "Transforming growth factor (TGF-beta) specific signaling by chimeric TGF-beta type II receptor with intracellular domain of activin type IIB receptor" J.Biol.Chem. 272 (34). 21187-21194 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakao, A., Imamura, T., Souchelnytskyi, S., Kawabata, M.Ishisaki, A., Oeda, E., Tamaki, K., Hanai, J.-i., Heldin, C.-H., Miyazono, K., and ten Dijke, P.: "TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4" EMBO J.16 (17). 5353-5362 (1997)
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[Publications] Imamura, T., Takase, M., Nishihara, A., Oeda, E., Hanai, J.-i., Kawabata, M.and Miyazono, K.: "Smad6 inhibits signalling by the TGF-beta superfamily" Nature. 389 (6651). 622-626 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Takenoshita, S., Mogi, A., Nagashima, M., Yang, K., Yagi, K., Hanyu, A., Nagamachi, Y., Miyazono, K., and Hagiwara, K.: "Characterization of MADH2/Smad2 gene, a human Mad homolog responsible for transforming growth factor-b and activin signal transduction pathway" Genomics. (in press). (1998)
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「研究成果報告書概要(欧文)」より
