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

• 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

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与多种蛋白质合成复合物，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是c-myc基因起源/增强子的DNA结合蛋白。MSSP起着DNA复制和转录因子的作用。MSSP通过其c端部分与C-MYC的n端部分结合。2) AMY-1利用两个杂交系统克隆了一个新的编码AMY-1的cDNA。AMY-1位于细胞核内，通过c -末端与C-MYC的n端区结合。AMY-1作为转录因子，刺激C-MYC的转录活性。AMY-1也显著刺激了C-MYC的转化活性。3)已知Pim-1能转化c-myc细胞。在这里，我们发现Pim-1与C-MYC直接相关。Pim-1通过过表达诱导细胞凋亡。Pim-1到C-MYC的信号转导可能参与凋亡通路。4) DNA聚合酶a和cdk2 （G1/S检查点蛋白蛋白）的催化亚基n端也结合了C-MYC和MSSP。MSSP刺激聚合酶活性。这些结果表明，MSSP/C-MYC在G1/S中起关键作用，特别是DNA复制的起始。

项目成果

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。”

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。”

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。”

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。”

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。”