X RAY, HEAT SHOCK AND CELL CYCLE COUPLED GENE EXPRESSION

描述：(改编自研究人员摘要)肿瘤细胞 电离辐射或热疗后的增殖 被认为是方案中治疗结果的主要决定因素 利用这些代理人。最近的研究表明，核扩散是 受细胞周期偶联基因的时间表达控制。这些 基因在多个水平上受到调控，包括转录和 转录后机制，如信使核糖核酸稳定性。整体而言 拟议研究的目的是阐明心力衰竭的发病机制。 X射线和高温诱导细胞周期下调的耦合作用 S晚期和G2期特有的基因。特别是这些调查人员 将检验这一假说，即信使核糖核酸稳定性在 拓扑异构酶IIα(Topo II)在这些条件下的表达。拓扑II 是复制过程中所需的多功能蛋白质，染色体 有丝分裂时的分离和其他与DNA相关的活动 改变DNA超级卷曲的能力。Topo II在S晚期表达最多 和G2期，并被x射线或热休克下调， 延缓细胞周期进程的条件。这一机制通过它 Topo II基因3‘端非翻译区的特定序列调节 周转率将被确定，与之相互作用的多肽 序列将被识别。最后，将确定是否增强了 Topo II mRNA的稳定性增加了相应的蛋白质水平，从而 导致了改变的G2-凌日。

DESCRIPTION: (adapted from the investigator's abstract) Tumor cell proliferation following treatment with ionizing radiation or hyperthermia is thought to be major determinant of therapeutic outcome in protocols utilizing these agents. Recent studies have shown that proliferation is controlled by the temporal expression of cell cycle coupled genes. These genes are regulated at multiple levels including both transcriptional and post-transcriptional mechanisms such as mRNA stability. The overall objective of the proposed research is to elucidate the mechanism of x-irradiation and hyperthermia-induced down regulation of cell cycle coupled genes specific to late S and G2-phases. Specifically these investigators will test the hypothesis that mRNA stability plays a significant role in the expression of topoisomerase IIalpha (TopoII) under these conditions. TopoII is a multifunctional protein required during replication, chromosome disjunction at mitosis and other DNA-related activities by virtue of its ability to alter DNA supercoiling. TopoII is maximally expressed in late S and G2- phases, and is down regulated by x-irradiation or heat shock, conditions which delay cell cycle progression. The mechanism by which specific sequences in the 3' untranslated region of the TopoII mRNA regulate turnover will be determined and the polypeptides which interact with those sequences will be identified. Finally, it will be determined if enhanced stability of TopoII mRNA increases the corresponding protein levels thus leading to altered G2-transit.