Analysis of the new nuclear factor mel-18 which affects the development and signaltransduction of B cells

影响B细胞发育和信号转导的新核因子mel-18分析

• 批准号: 07670365
• 负责人: KANNO Masamoto
• 金额: $ 1.47万
• 依托单位: Chiba University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670365/
• 关键词: cell cycle; signal transduction; antigen receptor; Polycomb group gene; ポリコム遺伝子; B細胞分化; 細胞増殖; c-myc; サイクリン

mel-18 is a mammalian homologue of the Drosophila Polycomb group (PcG) gene encoding a sequence-specific transcriptional repressor. We found that the overexpression of mel-18 causes the cell cycle arrest of B-cells after stimulation of the BCR.Molecular analysis revealed that the downregulation of cyclin D2, cyclin E,CDK4, CDK6, CDK7, and CDC25A causes the impaired activities of cyclin-dependent kinases, resulting in hypophosphorylation of the Rb protein. We also demonstrated that c-myc is a direct target of Mel-18 and is downregulated upon mel-18 overexpression. c-Myc is known to regulate positively the expression of cdc25a and cyclin E.Thus we conclude that mel-18 negatively regulates the cell cycle progression through a new cascade starting from mel-18 to c-myc then cdc25a or cyclin E.

MEL-18是编码序列特异性转录抑制剂的果蝇多康布基（PCG）基因的哺乳动物同源物。我们发现MEL-18的过表达导致BCR刺激后B细胞的细胞周期停滞。分子分析表明，细胞周期蛋白D2，Cyclin E，CDK4，CDK6，CDK6，CDK7和CDC25A的下调会导致受损的活性。细胞周期蛋白依赖性激酶，导致RB蛋白的下磷酸化。我们还证明了C-MYC是MEL-18的直接靶标，并且在MEL-18过表达下被下调。众所周知，C-MYC会积极调节Cdc25a和细胞周期蛋白的表达。我们得出的结论是，MEL-18通过从MEL-18到C-Myc，然后是CDC25A或Cyclin E的新级联反应负调节细胞周期的进展。

项目成果

Tetsu, O., Kanno, R., Isono, K., Taniguchi, M.and Kanno, M: "Cloning and characterization of two transcripts generated from the mel-13 gene positioned adjacent to the mammalian Polycomb group-related gene mel-18." Biochem.Biophys.Acta. 1305. 109-112 (1996

Tetsu, O.、Kanno, R.、Isono, K.、Taniguchi, M. 和 Kanno, M：“对位于哺乳动物 Polycomb 组相关基因 mel 附近的 mel-13 基因生成的两个转录物进行克隆和表征。

Akasaka,T.: "A role for mel-18, a Polycomb group-related vertebrate gene, during the anteroposterior specification of the axial skelton." Development. 122. 1513-1522 (1996)

Akasaka,T.：“mel-18（一种与 Polycomb 群相关的脊椎动物基因）在中轴骨骼的前后规范中的作用。”

Kanno,M.: "mel-18, a Polycomb group-related mammalian gene, encodes transcriptional negative reguiator with tumor suppressive activity" EMBO. J.14. 5672-5678 (1995)

Kanno,M.：“mel-18，一种与 Polycomb 组相关的哺乳动物基因，编码具有肿瘤抑制活性的转录负调节子”EMBO。

Tetsu,O.: "Cloning and characterization of two transcripts generated from the mel-13 gene positioned adiacent to the mammalian Polycomb group-related gene mel-18." Biochem. Biophys. Acta. 1305. 109-112 (1996)

Tetsu,O.：“对与哺乳动物 Polycomb 组相关基因 mel-18 相邻的 mel-13 基因生成的两个转录本进行克隆和表征。”

Tetsu,O.: "Cloning and characterization of two transcripts generated from the mel-13 gene positioned adjacent to the mammalian Polycomb group-related gene mel-18" Biochem.Biophys.Acta. 1305. 109-112 (1996)

Tetsu,O.：“从位于哺乳动物 Polycomb 组相关基因 mel-18 附近的 mel-13 基因生成的两个转录本的克隆和表征”Biochem.Biophys.Acta。