Novel regulation of rDNA transcription by mTOR/S6K signalling

mTOR/S6K 信号传导对 rDNA 转录的新调控

• 批准号: nhmrc : 251688
• 负责人: Prof Richard Pearson
• 金额: $ 26.26万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-regulation-rdna-mtors6k-signalling/95851
• 关键词: Novel; regulation; rDNA; transcription; mTOR

Increased cellular growth requires a number of important processes to occur, the most fundamental of which is protein synthesis. Successful synthesis of proteins requires a large number of efficient ribosomes, the protein synthesis machinery. mTOR is a central cellular signalling molecule that directly regulates growth via modulating the efficiency of the ribosomes. It does this by regulating an enzyme called S6 kinase. Interestingly for long term or sustained increases in the rates of growth an increase in the number of ribosomes in addition to an increase efficiency of protein synthesis is required. This proposal will test the hypothesis that the mTOR-S6 kinase signalling pathway regulates protein synthesis both at the level of ribosome efficiency and capacity. This will be extended to determine the mechanism by which such regulation occurs. Furthermore recent studies have demonstrated that S6 kinase is involved in tumor growth. We propose that S6 kinase will contribute to the regulation of both normal or tumor growth at least in part via modulation of the number of ribosomes. Accordingly, S6K is upregulated in a segregated proportion of breast tumors. Outcomes from this project have the potential to provide targets to which specific therapies for particular breast tumors can be developed. Overall this information will also extend our basic knowledge on normal growth regulation.

细胞生长的增加需要许多重要的过程发生，其中最基本的是蛋白质合成。蛋白质的成功合成需要大量高效的核糖体，即蛋白质合成机器。mTOR是通过调节核糖体的效率直接调节生长的中央细胞信号传导分子。它通过调节一种名为S6激酶的酶来实现这一点。有趣的是，对于生长速率的长期或持续增加，除了蛋白质合成效率的增加之外，还需要核糖体数量的增加。该提议将检验mTOR-S6激酶信号通路在核糖体效率和能力水平上调节蛋白质合成的假设。这将被扩展到确定这种调节发生的机制。此外，最近的研究表明，S6激酶参与肿瘤生长。我们建议，S6激酶将有助于正常或肿瘤生长的调节，至少部分通过调节核糖体的数量。因此，S6 K在乳腺肿瘤的分离比例中上调。该项目的成果有可能为特定乳腺肿瘤的特定治疗提供目标。总的来说，这些信息也将扩展我们对正常生长调节的基本知识。