MECHANISM OF TRANSFORMATION BY THE V-MYB ONCOGENE

本项目的目标是了解v-myb 禽成髓细胞瘤病毒（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c-myb的祖先， 在人类、小鼠和鸡中保存。其次，c-myb的改变导致 小鼠和鸟类的骨髓、红细胞和淋巴白血病。第三，c-myb 已经显示在各种人类中扩增和/或重排 恶性肿瘤。由v-myb和c-myb编码的蛋白质都存在 并与DNA结合。我们实验室最近的工作 这强烈表明这些myb编码的核蛋白通过调节 其他细胞基因的表达。本文中概述的研究 该提案将实现以下目标： （1）确定转化是否需要p48 v-myb的基因调控; （2）定义基因被调控所需的DNA序列， p48v-myb; （3）确定p48 v-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-蛋白质相互作用的作用 p48 v-myb在转化和基因调控中的作用; （5）确定DNA结合的结构和功能保守性 来自脊椎动物、无脊椎动物和绿色的myb相关蛋白的结构域 植物; （6）识别和表征由以下基因控制的细胞基因： p48v-myb。

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.