Molecular Mechanisms of Differentiation and Proliferation Switches

分化和增殖开关的分子机制

• 批准号: 05269102
• 负责人: KATSURA Isao
• 金额: $ 74.24万
• 依托单位: National Institute of Genetics (1994-1995)Kyoto University (1993)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05269102/
• 关键词: cell cycle; cell differentiation; cell proliferation; cyclin; cdk; phosphorylation; protein kinase; control mechanism; シグナル伝達; 細胞増殖制御; プロテインキナーゼ; プロテインフォスファターゼ; 転写因子

Research on the control mechanisms of cell-proliferation and cell-differentiation was performed from the viewpoint of cell-cycle, and the following results were obtained. (1) C.elegans hch-1 gene, which controls hatching and cell-migration, encodes a protein related to BMP-1 and TOLLOID (Katsura). (2) The MAPKK/MAPK cascade is necessary and sufficient for the initiation of Xenopus oocyte maturation (Nishida). (3) Cdc2 kinase, Ckinase and CF kinase were shown to phosphorylate intermediate filament proteins during the cell cycle, by using phosphoprotein-specific antibodies (Inagaki). (4) Expression of DELTAFosB in quiescent cells initiates cell proliferation through increase of cyclin E and CDK2 mRNAs by decrease of their degradation rate (Nakabeppu). (5) Replication factor C is involved in the S phase check-point control, because a ts mutation in its subunit gene RFC5 is suppressed by the overproduction of SPK1/Rad53 kinase (Sugimoto). (6) epi-1, a gene specific for the growth arrest of human epithelial cells, resembles warts/large tumor suppressor, a Drosophila tumor suppressor gene (Masui). (7) Human cDNAs of a new TGF-beta receptor subtype, a 14-4-3 protein and a novel protein HCP1, enhance the transcription of inositol-synthesizing enzymes in yeast cells (Nikawa). The results obtained by diverse materials and methods revealed the basic and species-specific mechanisms of the switches in cell-proliferation/differentiation.

从细胞周期的角度对细胞增殖和细胞分化的调控机制进行了研究，并获得了以下结果。(1)秀丽隐杆线虫hch-1基因编码一种与BMP-1和TOLLOID（Katomyloid）相关的蛋白质，控制细胞的孵化和迁移。(2)MAPKK/MAPK级联反应是启动非洲爪蟾卵母细胞成熟所必需的。(3)通过使用磷蛋白特异性抗体（Inagaki），显示Cdc 2激酶、C激酶和CF激酶在细胞周期期间使中间丝蛋白磷酸化。(4)DELTAFosB在静止细胞中的表达通过降低细胞周期蛋白E和CDK 2 mRNA的降解速率而增加细胞周期蛋白E和CDK 2 mRNA来启动细胞增殖（Nakabeppu）。(5)复制因子C参与S期检查点控制，因为其亚基基因RFC 5中的ts突变被SPK 1/Rad 53激酶（Sugimoto）的过量产生抑制。(6)epi-1是一种特异于人上皮细胞生长停滞的基因，类似于疣/大肿瘤抑制基因，一种果蝇肿瘤抑制基因（Masui）。(7)一种新的TGF-β受体亚型，一种14-4-3蛋白和一种新的蛋白HCP 1的人cDNA增强了酵母细胞中肌醇合成酶的转录（Nikawa）。通过多种材料和方法获得的结果揭示了细胞增殖/分化开关的基本和种属特异性机制。

项目成果

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K.Doi 等人：“MSG5，一种新型蛋白磷酸酶促进酿酒酵母对信息素反应的适应”EMBO J.13。

Takashi Toda: "Isolation and characterization of the fission yeast protein phosphatase gene ppel+involved in cell shape control and mitosis." Mol.Biol.Cell.4. 303-313 (1993)

Takashi Toda：“参与细胞形状控制和有丝分裂的裂殖酵母蛋白磷酸酶基因 ppel 的分离和表征。”

Y.Takai et al.: "Mitosis-specific phosphorylation of vimentin by protein kinase C coupled with reorganization of intracellularmembranes." J.Cell Biol.133. 141-149 (1996)

Y.Takai 等人：“蛋白激酶 C 对波形蛋白的有丝分裂特异性磷酸化与细胞内膜的重组相结合。”

M.Sekimata et al.: "Detection of protein kinase activity specifically activated at metaphase-anaphase transition." J.Cell Biol.132. 635-641 (1996)

M.Sekimata 等人：“检测在中期-后期转变时特异激活的蛋白激酶活性。”

H.Kosako et al.: "Requirement for the MAP kinase kinase/Map kinase cascade in Xenopus oocyte maturation" EMBO J.13. 2131-2138 (1994)

H.Kosako 等人：“爪蟾卵母细胞成熟中 MAP 激酶激酶/MAP 激酶级联的要求”EMBO J.13。