Tor Signal Transduction to Gene Expression

Tor 信号转导至基因表达

• 批准号: 6431058
• 负责人: STEVEN ZHENG
• 金额: $ 29.95万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6431058
• 关键词: biological signal transduction; drug interactions; fungal genetics; gene expression; gene mutation; multidrug resistance; nitrogen metabolism; phosphorylation; protein kinase; protein structure function; sirolimus; site directed mutagenesis; transcription factor; yeasts

DESCRIPTION (provided by applicant): Raparnycin is a potent immunosuppressive antibiotic currently being used for kidney transplants. It is also under clinical trials for transplantation of other organs as well as treatment of leukemia. When complexed with its immunophilin receptor FKBP12, rapamycin binds to and inhibits Tor, the target of raparnycin protein, an intracellular signaling kinase essential for cell growth and functions. However, the overall biological functions of Tor remain poorly understood. Our long-term goal is to understand the cellular functions of Tor and how rapamycin interferes with different aspects of Tor functions. Tor is highly conserved throughout eukaryotic kingdom. Thus, study of Tor in yeast should provide new important insights into the mechanism of Tor signaling. This knowledge should also contribute to the overall understanding of the basic control of cell growth and proliferation, and help evaluate additional benefits as well as potential side effects of rapamycin as a transplantation medicine. In this proposal, we will examine several new aspects of Tor functions. Specifically, we will examine the mechanism of signaling by Tor leading to control of transcription in response to extracellular and intracellular cues. Accomplishment of these research objectives may have significant implications in transplantation medicine as well as understanding and treatment of metabolic disorders, cancer and fungal infection.

性状（由申请方提供）：拉帕霉素是一种强效免疫抑制剂， 目前用于肾脏移植的抗生素。国还有 其他器官移植以及治疗 白血病当与其亲免素受体FKBP 12复合时，雷帕霉素结合 并抑制雷帕霉素蛋白的靶点Tor， 细胞生长和功能所必需的信号激酶。但整体 Tor的生物学功能仍然知之甚少。我们的长期目标是 了解Tor的细胞功能以及雷帕霉素如何干扰 Tor功能的不同方面。Tor是高度保守的 真核生物界因此，Tor在酵母中的研究将提供新的重要 深入了解Tor信号的机制。这些知识也应该 有助于全面了解细胞生长的基本控制， 扩散，并帮助评估额外的好处以及潜在的一面 雷帕霉素作为移植药物的效果。在本提案中，我们将 检查Tor功能的几个新方面。具体来说，我们将研究 Tor的信号传导机制导致响应中的转录控制 细胞外和细胞内的线索。这些研究成果 目标可能对移植医学有重要意义， 以及了解和治疗代谢紊乱、癌症和真菌 感染