MECHANISM OF TRANSFORMATION BY THE V-MYB ONCOGENE

V-MYB 癌基因的转化机制

• 批准号: 3185817
• 负责人: Joseph Steven Lipsick
• 金额: $ 15.93万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-03-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185817
• 关键词: DNA binding protein; avian leukosis virus; chickens; disease /disorder model; gene deletion mutation; gene mutation; genetic mapping; genetic regulation; genetic regulatory element; genetic transcription; laboratory rabbit; molecular cloning; mutant; neoplasm /cancer genetics; oncogenes; oncoproteins; phosphorylation; protein structure function; protooncogene; tissue /cell culture; viral leukemogenesis; virus genetics; virus protein

The goal of this project is to understand the mechanism by which the v-myb oncogene of avian myeloblastosis virus (AMV) induces acute myeloid leukemia. This system provides a valuable model for human leukemogenesis for several reasons. First, progenitor of this oncogene, c-myb, is highly conserved in humans, mice and chickens. Second, alterations in c-myb cause myeloid, erythroid, and lymphoid leukemias in mice and birds. Third, c-myb has been shown to amplified and/or rearranged in various human malignancies. The proteins encoded by both v-myb and c-myb are present within the cell nucleus and bind to DNA. Recent work in our laboratory strongly suggests that these myb-encoded nuclear proteins act by regulating the expression of other cellular genes. The studies outlined in this proposal will accomplish the following: (1)Determine if gene regulation by p48v-myb is required for transformation; (2)Define the DNA sequences required for a gene to be regulated by p48v-myb; (3)Determine which domains of p48v-myb are required for gene regulation; (4)Determine the role of phosphorylation and protein-protein interactions in transformation and gene regulation by p48v-myb; (5)Determine the structural and functional conservation of the DNA-binding domains of myb-related proteins from vertebrates, invertebrates, and green plants; (6)Identify and characterize the cellular genes which are controlled by p48v-myb.

这个项目的目标是了解v-myb 禽成髓细胞增生症病毒(AMV)癌基因诱导急性髓系白血病 白血病。该系统为人类白血病的发生提供了一个有价值的模型。 有几个原因。首先，这种癌基因的前体c-myb高度依赖于 在人类、小鼠和鸡中保存。第二，c-myb的变化导致 小鼠和鸟类的髓系、红系和淋巴细胞性白血病。第三，c-MYB 已经被证明在不同的人类中被扩增和/或重排 恶性肿瘤。同时存在v-myb和c-myb编码的蛋白质。 在细胞核内并与DNA结合。我们实验室最近的工作 强烈表明这些MYB编码的核蛋白通过调节 其他细胞基因的表达。这篇文章中概述的研究 提案将实现以下目标： (1)确定转化是否需要p48v-myb的基因调控； (2)定义基因受调控所需的DNA序列 P48V-MYB； (3)确定p48V-MYB的哪些结构域是基因调控所必需的； (4)确定磷酸化和蛋白质相互作用的作用 P48v-myb的转化和基因调控； (5)确定DNA结合的结构和功能保守性 脊椎动物、无脊椎动物和绿色动物MYB相关蛋白的结构域 植物； (6)鉴定和鉴定受控制的细胞基因 P48v-MYB。