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Conservative regulation of DNA replication and transcription in mammalian cells

哺乳动物细胞中 DNA 复制和转录的保守调控

基本信息

批准号：
06454591
负责人：
ARIGA Hiroyoshi
金额：
$ 4.54万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454591/
关键词：
C-MYC DNA BINDING TRANSCRIPTION FACTOR APOPTOSIS TRANSFORMATION CELL CYCLE N-myc DNA複製転写調節トランスフォーメーション hsp70 MHC classI

项目摘要

C-MYC is making complex with a variety of proteins to play numerous roles. We have identified and cloned cDNAs encoding MYC-binding proteins.1) MSSP MSSP was found as an DNA binding protein on origin/enhancer in c-myc gene. MSSP plays a role as DNA replication and transcription factor. MSSP binds to N-terminal portion of C-MYC via its C-terminus portion.2) AMY-1 Using two hybrid system we cloned a novel cDNA encoding AMY-1. AMY-1 was located in the nucleus, and bound to N-terminal region of C-MYC via its C-terminus. AMY-1 acted as a transcription factor and stimulated transcriptional activity of C-MYC.AMY-1 also stimulated C-MYC's transforming activity dramatically.3) Pim-1 Pim-1 was known to transform cells with c-myc. Here we found that Pim-1 was directly associated with C-MYC.Pim-1 induced apoptosis by its overexpression. Signal transduction from Pim-1 to C-MYC may contribute apoptosis pathway.4) DNA polymerase a and cdk2 C-MYC and MSSP were also bound to N-terminal portion of catalytic subunit of DNA polymerase a and cdk2, a protein for G1/S checkpoint protein. MSSP stimulated polymerase activity. These results indicated that MSSP/C-MYC play a key role G1/S,especially the initiation of DNA replication.

C-MYC 与多种蛋白质形成复合物，发挥多种作用。我们已经鉴定并克隆了编码MYC结合蛋白的cDNA。1)MSSP MSSP被发现是c-myc基因的起源/增强子上的DNA结合蛋白。 MSSP起到DNA复制和转录因子的作用。 MSSP 通过其C 末端部分与C-MYC 的N 末端部分结合。2) AMY-1 使用两个杂交系统，我们克隆了编码AMY-1 的新cDNA。 AMY-1位于细胞核中，通过其C末端与C-MYC的N末端区域结合。 AMY-1作为转录因子，刺激C-MYC的转录活性。AMY-1还显着刺激C-MYC的转化活性。3)Pim-1 Pim-1已知可以转化c-myc细胞。在这里我们发现Pim-1与C-MYC直接相关。Pim-1通过其过表达诱导细胞凋亡。从Pim-1到C-MYC的信号转导可能有助于细胞凋亡途径。4)DNA聚合酶a和cdk2 C-MYC和MSSP也与DNA聚合酶a和cdk2（G1/S检查点蛋白的一种蛋白）催化亚基的N端部分结合。 MSSP 刺激聚合酶活性。这些结果表明MSSP/C-MYC在G1/S尤其是DNA复制的启动中起关键作用。