Growth Control and Anti-Cancer Mechanisms

生长是通过积累新合成的蛋白质来增加细胞质量和大小的过程。它是 越来越被认为是肿瘤发生过程中的一个重要过程，这是支持快速 癌细胞增殖(细胞数量增加)。蛋白质合成的速度由两者决定。 翻译起始和核糖体的丰度。生产核糖体或核糖体生物发生 涉及数百个基因和所有三种RNA多聚酶，占核转录的90%。 核糖体的生物合成是高耗能的，并且受到生长因子和营养物质的严格控制。它 人们早就知道，在癌细胞中，翻译机制的组件被解除管制或 表达错误。一些肿瘤抑制基因和原癌基因，如视网膜母细胞瘤(Rb)蛋白， P53、PTEN和Myc是核糖体生物发生的靶点。雷帕霉素是一种很有前途的新药物 目前正在进行大规模临床试验的抗癌药物。耐受性良好，并显示出良好的疗效 许多人类癌症。我们最近获得的证据表明，抑制核糖体生物发生是至关重要的 针对雷帕霉素抑制细胞生长，发现了雷帕霉素抑制细胞生长的几种新机制 核糖体生物发生。在这项计划中，我们将研究核糖体的调节机制。 生物发生、核仁大小控制和雷帕霉素抑制。这些目标的实现应该会取得进展 对雷帕霉素的生长控制、肿瘤发生和作用机制的理解。另外， 这样的研究可能会导致更有效的抗癌治疗策略，并有助于发现新的抗癌药物 癌症治疗学中这一重要但研究很少的领域的靶点。

Growth is the process to increase cell mass and size by accumulation of newly synthesized proteins. It is increasingly appreciated as an important process in tumorigenesis, which is required to support the rapid cancer cell proliferation (an increase in cell number). The rate of protein synthesis is determined by both translational initiation and the abundance of ribosomes. Producing ribosomes or ribosome biogenesis involves several hundred genes and all three RNA polyrinerasesand accounts for 90% nuclear transcription. Ribosome biogenesis is highly energy-consuming and is tightly controlled by growth factors and nutrients. It has been long known that, in cancer cells, components of the translational machinery are deregulated or misexpressed. Several tumor suppressors and proto-oncogenes, such as the retinoblastoma (Rb) protein, p53, PTEN and Myc, have been shown to target ribosome biogenesis. Rapamycin is a promising new anticancer drug currently under large clinical trials. It is well tolerated and has shown excellent efficacy for many human cancers. We have recently obtained evidence that inhibition of ribosome biogenesis is crucial for rapamycin to inhibit cell growth, and discovered several new mechanisms for rapamycin to inhibit ribosome biogenesis. In this proposal, we will investigate the regulatory mechanisms of ribosome biogenesis, nucleolar size control and rapamycin inhibition. Accomplishment of these goals should advance the understanding of growth control, tumorigenesis and the mechanism of action by rapamycin. Additionally, such studies may lead to more effective anticancer therapeutic strategies and help identify new cancer drug targets in this important yet poorly studied area in cancer therapeutics.