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 组； DNA 复制 (MSSP)、转录 (AMY-1、MM-1.CBF)、细胞周期控制 (p21) 和细胞凋亡诱导 (Pim-1) 的因子。在这些蛋白质中，MSSP 进一步与 DNA 聚合酶 α 和 PCNA 直接相互作用，并与 cdk2 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。一种新型蛋白AMY-1与C-MYC的N端（即所谓的反式激活结构域）相互作用，刺激C-MYC的转录活性。AMY-1在G1/S转变后从细胞质易位到细胞核。 Pim-1是丝氨酸/苏氨酸激酶，其靶蛋白被鉴定为PAP-1。 Pim-1 还磷酸化 CDC25，CDC25 的基因已知是 C-MYC 的转录靶标。这些结果表明，C-MYC 的多种功能是在细胞周期期间由一种独特的蛋白质复合物实现的。

项目成果

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Pogonec,P：“bHLHZip USF 和 bZip Fral 蛋白之间的跨家族相互作用”癌基因。