INTERACTION OF ONCOGENES WITH AVIAN ERYTHROID CELLS

造血系统在人的一生中都在发挥作用 产生髓系、红系和淋巴系细胞的动物 血统。动态平衡是由信号调节的 细胞增殖和/或分化为特定细胞的能力 血统。白血病可以被视为一种疾病，由 这些相互作用的崩溃。癌基因通过以下途径导致白血病 干扰细胞的正常调节机制，并在这样做的过程中 影响细胞的分化和/或增殖能力 细胞。我们的目标是了解癌基因产品是如何 与这些正常的调节机制相互作用会导致白血病。 禽红母细胞增多症病毒对红系细胞的转化 AEV S13株为癌基因研究提供了强大的模型系统 影响禽类分化和/或增殖的因素 红系细胞。使用这个系统，我们有两个主要目标： 从病毒学角度了解S13病毒的转化机制 编码癌基因v-SEA，并使用温度条件突变体 在海洋中癌基因与其他癌基因的结合研究 这些影响红系的癌基因的作用机制 转型分化而不具有增殖性 导致红细胞增多症的能力。具体来说，我们有 以下目标： 1.突变v-SEA癌基因以确定重要的功能 它们转化细胞的能力所必需的区域。 将产生突变体以解决 自动磷酸化，细胞内定位，多聚体， 和C-末端调控结构域的转换。 2.细胞SEA基因产物的鉴定及分离 该基因的全长cDNA克隆。将会产生突变体 确定c-SEA基因被激活的机制 以致于它引起了变化。 3.将ts-SEA癌基因与v-Rel结合使用 或v-ski癌基因来确定这两种基因 核癌基因影响红系分化。这些 机制将与我们之前确定的机制进行比较 涉及v-erba癌基因和转铁蛋白受体。

The hematopoietic system functions throughout the lifetime of an animal to produce cells of the myeloid, erythroid, and lymphoid lineages. Homeostasis is maintained by signals that regulate the cell's ability to proliferate and/or differentiate into the specific lineages. Leukemia can be viewed as a disease resulting from a breakdown in these interactions. Oncogenes cause leukemia by perturbing the cell's normal regulatory mechanisms, and in doing so influence the differentiation and/or proliferative capacity of the cells. Our objective is to understand how oncogene products interact with these normal regulatory mechanisms to cause leukemia. Erythroid cell transformation by the avian erythroblastosis virus (AEV) strain S13 provides a powerful model system to study oncogenes that affect the differentiation and/or proliferation of avian erythroid cells. Using this system we have two major objectives: to understand the mechanism of transformation of the S13 virally encoded oncogene v-sea, and to use a temperature-conditional mutant in the sea oncogene in combination with other oncogenes to study the mechanism of action of these oncogenes that affect erythroid transformation and differentiation but do not have the proliferative capability to cause erythroblastosis. Specifically we have the following aims: 1. To mutate the v-sea oncogene to identify functionally important regions that are necessary for their ability to transform cells. Mutants will be generated to address the importance of autophosphorylation, intracellular localization, multimerization, and C-terminal regulatory domains in transformation. 2. To characterize the cellular sea gene product and isolate full-length cDNA clones for this gene. Mutants will be generated to identify the mechanisms by which the c-sea gene can be activated such that it causes transformation. 3. To use the ts-sea oncogene in combination with either the v-rel or v-ski oncogenes to determine the mechanisms by which these two nuclear oncogenes affect erythroid differentiation. These mechanisms will be compared with those we have previously identified involving the v-erbA oncogene and the transferrin receptor.