Regulation of ribosome biogenesis during the cell cycle, stress and cellular transformation

细胞周期、应激和细胞转化过程中核糖体生物发生的调节

• 批准号: G0501666/1
• 负责人: Nicholas Watkins
• 金额: $ 45.21万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501666%2F1
• 关键词: Regulation; ribosome; biogenesis; during; cell

One basic feature of cells is their ability to grow and divide. The production of proteins, essential cell components that represent a significant proportion of the cell mass, is essential for cell growth. The ribosome is a molecular factory in the cell responsible for the synthesis of proteins. The cell regulates protein production by changing the activity and/or the levels of ribosomes. In cell transformation, the initial stage in the generation of tumours, the basic regulation of cell growth and division is lost allowing the cell to continue growing unchecked. It has recently been shown that many proteins that either cause or regulate cancer are also linked to the regulation of protein synthesis in the cell. This often involves the regulation of the synthesis of new ribosomes in a specific compartment in the cell known as the nucleolus. The production of the ribosome is a highly complicated process that is at present poorly understood. The cell has natural tumour suppressive agents such as the protein p53. The activation of this protein inhibits cell growth and division and is linked to the function of the nucleolus. We have found that chemical inhibitors that activate p53 also block the production of ribosomes. We propose to investigate the mechanisms by which these inhibitors block to production of ribosomes. The information gained from this approach will provide important information on how the cell activates the tumour suppressor p53. This research will provide important information on how the cell regulates cell growth and division and should provide new targets for anti-cancer therapeutics.

细胞的一个基本特征是它们生长和分裂的能力。蛋白质的产生是细胞生长所必需的，蛋白质是细胞的基本成分，占细胞质量的很大比例。核糖体是细胞中负责蛋白质合成的分子工厂。细胞通过改变核糖体的活性和/或水平来调节蛋白质的产生。在细胞转化中，即肿瘤产生的初始阶段，细胞生长和分裂的基本调节丧失，允许细胞继续不受抑制地生长。最近的研究表明，许多引起或调节癌症的蛋白质也与细胞中蛋白质合成的调节有关。这通常涉及细胞中称为核仁的特定隔室中新核糖体合成的调节。核糖体的产生是一个非常复杂的过程，目前人们对这个过程还知之甚少。该细胞具有天然的肿瘤抑制剂，如蛋白质p53。这种蛋白质的激活抑制细胞生长和分裂，并与核仁的功能有关。我们发现激活p53的化学抑制剂也会阻断核糖体的产生。我们建议研究这些抑制剂阻断核糖体产生的机制。从这种方法中获得的信息将提供有关细胞如何激活肿瘤抑制因子p53的重要信息。这项研究将为细胞如何调节细胞生长和分裂提供重要信息，并为抗癌治疗提供新的靶点。