SV40-INDUCED CHANGES IN GROWTH REGULATION IN HOST CELLS

本研究的目的是了解这一机制(S) S期特异性基因在正常和SV40中的调控 被感染的细胞。因为这些基因的表达是相关的 随着细胞的生长状态，希望能对 他们的监管将有助于理解控制 在正常细胞和病毒感染细胞中的细胞生长。这 理解这一点反过来对致癌基因的研究也很重要。 转化，因为转化细胞的属性之一是 他们未能以正常的方式调控自己的成长。 S相规律的研究方法 特定的基因将是一个分子基因，使用胸苷激酶 (TK)基因作为模型系统。TK在体内的表达受调控 细胞周期，在G0和G1期细胞中较低，而在G0和G1期细胞中增加 随着细胞进入S期。基因组和cDNATK克隆 将用于构建一系列突变型和杂交型TK基因。 这些改变后的基因将被导入组织培养。 细胞，以及它们表达的调节将被检测。 使用这些技术，关于TK的以下问题 监管将被解决：1)在什么层面上监管 基因发生(转录/转录后等)？2) 哪些TK DNA序列负责这一调节？3) 病毒蛋白在诱导TK基因中起什么作用？4) 什么细胞因素参与了TK的诱导 吉恩？

The objective of this research is to understand the mechanism(s) by which S-phase specific genes are regulated in normal and SV40- infected cells. Since the expression of these genes is correlated with the growth state of the cell, it is hoped that an understand of their regulation will contribute to an understanding of the control of cell growth in normal and virus-infected cells. This understanding will in turn be important to the study of oncogenic transformation, since one of the properties of transformed cells is that they fail to regulate their growth in a normal way. The approach taken to investigating the regulation of S-phase specific genes will be a molecular one, using the thymidine kinase (TK) gene as a model system. TK expression is regulated during the cell cycle, being low in G0 and G1 phase cells, and increasing as the cells enter S phase. Both genomic and cDNA TK clones will be used to construct a series of mutant and hybrid TK genes. These altered genes will then be transfected into tissue culture cells, and the regulation of their expression will be examined. Using these techniques, the following questions concerning TK regulation will be addressed: 1) At what levels does regulation of the gene occur (transcriptional/post-transcriptional, etc.)? 2) What TK DNA sequences are responsible for this regulation? 3) What is the role of viral proteins in inducing the TK gene? 4) What cellular factor or factors are involved in inducing the TK gene?