HUMAN DBL ONCOGENE PRODUCT

人类 DBL 癌基因产品

基本信息

批准号：
3458623
负责人：
SHIV SRIVASTAVA
金额：
$ 8.5万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-03-01 至 1994-02-28
项目状态：
已结题

项目摘要

Cellular transforming genes have been identified in various human malignancies by DNA-mediated gene transfer using mouse NIH/3T3 cells as recipient. The db1 oncogene was detected as a transforming gene of human diffuse B-cell lymphoma. By molecular hybridization, db1 lacks detectable homology to other cellular or retroviral oncogenes. Intensive studies on the functions of number of transforming genes and their encoded proteins are beginning to reveal a close relationship between basic control signals governing cell transformation and normal cell proliferation. Therefore, it is of great interest to study the structure and functions of the protein encoded by a novel human oncogene, such as db1. We have identified a protein of about 66,000 daltons as the product of db1 oncogene. Preliminary subcellular localization studies revealed that P66 is a cytoplasmic protein distributed between cytosol and membrane fractions. Moreover, P66 is a phosphoprotein with phosphorylation being specific to serine residues. The present studies propose to pursue the characterization of P66 with a long term goal to understand its role in cellular transformation. Initial studies are aimed at characterizing the biosynthesis, precise subcellular localization and native configuration of db1 P66 which are pivotal to the understanding of its function. P66 phosphorylation will be characterized further to evaluate the regulatory effects of various growth factors and pharmacological agents. One of the aims of the studies presented here also includes the identification of the normal homologue of db1 P66. A comparison of the properties of normal db1 protein and P66 should provide information about the mechanisms of its acquired transforming potential. Furthermore, the distribution and levels of db1 protein will be evaluated in human neoplasms.

细胞转化基因已在多种人类中被发现使用小鼠进行 DNA 介导的基因转移治疗恶性肿瘤 NIH/3T3 细胞作为受体。 db1癌基因被检测为人弥漫性B细胞淋巴瘤的转化基因。经过分子杂交，db1 与其他基因缺乏可检测的同源性细胞或逆转录病毒癌基因。深入研究转化基因数量及其编码的功能蛋白质开始揭示基本之间的密切关系控制细胞转化和正常细胞的控制信号增殖。因此，研究该问题具有很大的兴趣新型人类编码蛋白质的结构和功能癌基因，例如db1。我们已经鉴定出一种蛋白质 66,000 道尔顿是 db1 癌基因的产物。初步的亚细胞定位研究表明 P66 是一种细胞质蛋白质分布在细胞质和膜部分之间。此外，P66是一种磷酸化的磷蛋白特定于丝氨酸残基。目前的研究建议追求 P66 的特征与长期目标的理解它在细胞转化中的作用。初步研究的目的是表征生物合成、精确的亚细胞定位和 db1 P66 的本机配置，这对于了解其功能。 P66 磷酸化将进一步表征以评估监管效果各种生长因子和药物。中的一个这里提出的研究目的还包括确定 db1 P66 的正常同源物。比较正常 db1 蛋白和 P66 的特性应提供有关其获得性转化机制的信息潜在的。此外，db1蛋白的分布和水平将在人类肿瘤中进行评估。