Molecular mechanism of cell proliferation and appoptosis by the actions of transcription/replication factors in mammalian cells.

哺乳动物细胞中转录/复制因子作用的细胞增殖和凋亡的分子机制。

• 批准号: 08457599
• 负责人: ARIGA Hiroyoshi
• 金额: $ 4.99万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457599/
• 关键词: MYC; cell transformation; cell cycle; apoptosis; transcroption; DNA replication; c-myc; 転写因子; cDNAクローニング; 癌遺伝子

We have identified several proteins that interact with C-MYC.These were classified to 4 group ; factor for DNA replication (MSSP), for transcription (AMY-1, MM-1. CBF), for cell-cycle control (p21), and for apoptosis induction (Pim-1). Of the proteins, MSSP futrher interacts with DNA polymerase alpha and PCNA directly, and cdk2 indirectly. C-MYC interacts with PCNA-binding region of p21 to rescue the inhibition of DNA replication by p21. A novel protein AMY-1 interacts the N-terrninal, so called transactivation domain of C-MYC,to stimulate transcriptional activity of C-MYC.AMY-1 was translocated from cytoplasm to nucleus after G1/S transition. Pim-1 is serine/threonine kinase and its target protein was identified, PAP-1. Pim-1 also phosphorylates CDC25 whose gene is known to be a transcriptional targer of C-MYC.These results suggest that a versatile functions of C-MYC occur by a distinguished protein complex during cell cycle.

我们已经鉴定了几种与C-MYC相互作用的蛋白质，这些蛋白质被分为4类：DNA复制因子（MSSP），转录因子（AMY-1，MM-1）。CBF）、细胞周期控制（p21）和凋亡诱导（Pim-1）。其中MSSP与DNA聚合酶α和PCNA直接相互作用，与cdk 2间接相互作用。C-MYC与p21的PCNA结合区相互作用，以挽救p21对DNA复制的抑制。新发现的AMY-1蛋白与C-MYC蛋白的N端（即反式激活结构域）相互作用，通过G1/S转换后从细胞质转移到细胞核，从而激活C-MYC蛋白的转录活性。Pim-1是丝氨酸/苏氨酸激酶，其靶蛋白PAP-1已被鉴定。Pim-1还磷酸化C-MYC的转录靶基因CDC 25，这些结果表明C-MYC在细胞周期中通过独特的蛋白质复合物发挥多种功能。

项目成果

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Taira, T.：“在人类热休克蛋白中鉴定出一种新型 G1/S 特异性增强子”Nucleic Acids Res.25。

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