1995 Fiscal Year Final Research Report Summary
Molecular mechanisms of retinoic acid-mediated control of cellular proliferation and differentiation
Project/Area Number |
06807014
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Pathological medical chemistry
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Research Institution | Osaka University |
Principal Investigator |
TAKIHARA Yoshihiro Research Institute for Microbial Diseases, Department of Medical Genetics, Associate Professor, 微生物病研究所, 助教授 (60226967)
|
Co-Investigator(Kenkyū-buntansha) |
NOMURA Midori Research Institute for Microbial Diseases, Department of Medical Genetics, Resea, 微生物病研究所, 助手 (60263315)
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Project Period (FY) |
1994 – 1995
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Keywords | F9 / retinoic acid / 14-3-3 / polyhomeotic / knockout mouse |
Research Abstract |
By using the differential hybridization methods, we isolated the 20 kinds of cDNA clones, whose expression is induced during RA-mediated F9 cell differentiation. Focusing on the following two clones, we analyzed the structure and function of the genes. (1) Rae12 : the rae12 gene family encodes at least 5 kinds of different 14-3-3 protein members, whose expression is induced during RA-mediated F9 cell differentiation. We showed the expression of these members enhance the Raf-1 kinase. Furthermore, we demonstrated the following points : i) overexpression of 14-3-3 proteins enhances the signal transduction in the MAP kinase cascade, resulting in the stimulated cellular proliferation and tumorigenic transformation of NIH 3T3 cells. ii) the induced expression of 14-3-3 proteins enhances the signal transduction in the MAP kinase cascade, that plays an important role during RA-mediated F9 cell differentiation. (2) Rae28 : structure analysis the cDNA clone suggested that the rae28 gene is a mammalian homologue of a Drosophila polyhometic gene. We isolated the rae28 gene and established the rae28 knockout mice. The homozygotes are lethal and showed the following intriguing phenotypes : i) heart malformations, ii) ophthalmic abnormalities, iii) skeletal abnormalities (posterior transformation) , iv) cleft palate.
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Research Products
(6 results)