Novel regulation of rDNA transcription by mTOR/S6K signalling

促进细胞生长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，这是蛋白质合成的机械。MTOR是一种中央细胞信号分子，通过调节核糖体的效率直接调节生长。它通过调节一种名为S6激酶的酶来实现这一点。有趣的是，为了长期或持续地提高增长速度，除了提高蛋白质合成效率外，还需要增加核糖体的数量。这一提议将检验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。这将扩大到确定这种监管发生的机制。此外，最近的研究表明，S6激酶参与了肿瘤的生长。我们认为，S6激酶将有助于调节正常或肿瘤的生长，至少部分是通过调节核糖体的数量。因此，S6K在单独比例的乳腺肿瘤中上调。该项目的成果有可能提供针对特定乳腺肿瘤的特定治疗方法的目标。总体而言，这些信息还将扩大我们对正常生长调控的基本知识。

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.