Conservative regulation of DNA replication and transcription in mammalian cells
Conservative regulation of DNA replication and transcription in mammalian cells
批准号:
06454591
负责人:
ARIGA Hiroyoshi
金额:
$4.54万
依托单位:
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
项目状态:
已结题
起止时间:
1994 至 1995
中文摘要
C-MYC与多种蛋白质形成复合物,发挥多种作用。1)MSSP MSSP是c-myc基因起始/增强子上的DNA结合蛋白。MSSP作为DNA复制和转录因子发挥作用。2)AMY-1利用双杂交系统克隆了编码AMY-1的新cDNA。AMY-1定位于细胞核内,通过C端与C-MYC的N端结合。3)Pim-1 Pim-1能转化c-myc细胞,并能促进c-myc的转化。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。4)DNA聚合酶a和cdk 2与C-MYC和MSSP的结合位点均位于DNA聚合酶a催化亚基的N端,与G1/S检查点蛋白cdk 2的结合位点也位于C-MYC和MSSP的N端。MSSP刺激聚合酶活性。这些结果表明MSSP/C-MYC在G1/S期起着关键作用,尤其是在DNA复制的启动过程中。
英文摘要
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.
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Taira, T.: "Autonomously replicating segment identified in the murine p53 gene contains p53 recognition sequence and bending region." Int. J. Onc.7. 115-122 (1995)
Taira, T.:“在鼠 p53 基因中鉴定出的自主复制片段包含 p53 识别序列和弯曲区域。”
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Iwata,K.: "Diversity of sites for measles virus binding and for inactivation of complement C3b and C46 on membrane confactor protein CD46." J.Biol.Chem.270. 15148-15152 (1995)
Iwata,K.:“麻疹病毒结合位点的多样性以及膜辅因子蛋白 CD46 上补体 C3b 和 C46 失活的位点多样性。”
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Taira,T.: "Autonomously replicating segment identified in the murine p53 gene contains p53 recognition sequence and bending region." Int.J.Onc.7. 115-122 (1995)
Taira,T.:“在鼠 p53 基因中鉴定出的自主复制片段包含 p53 识别序列和弯曲区域。”
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Takahashi,C.: "Involvement of PIM-1 in DNA fragmentation in mous NS-1-derived cells." Biochem Biophys.Res.Commun.215. 538-546 (1995)
Takahashi,C.:“PIM-1 参与小鼠 NS-1 衍生细胞的 DNA 片段化。”
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Manabe,A.: "Transcriptional repression activity of N-myc protein requires phosphorylation by MAP kinase." Biochim Biophys.Res.Commun.in press.
Manabe,A.:“N-myc 蛋白的转录抑制活性需要 MAP 激酶磷酸化。”
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