X RAY, HEAT SHOCK AND CELL CYCLE COUPLED GENE EXPRESSION

描述：（改编自研究者摘要）肿瘤细胞 用电离辐射或热疗治疗后的增殖， 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， 由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mRNA稳定性。 整体 这项研究的目的是阐明 X射线照射和高血压诱导的细胞周期下调 晚期S期和G2期特异性基因。 特别是这些调查员 将检验mRNA稳定性在细胞凋亡中起重要作用的假设。 在这些条件下表达拓扑异构酶II α（TopoII）。 topoii 是一种多功能蛋白质，在复制过程中，染色体 在有丝分裂和其他DNA相关的活动，凭借其 改变DNA超螺旋的能力 TopoII在晚期S 和G2相，并且通过X-照射或热休克下调， 延缓细胞周期进程的条件。 的机制 TopoII mRNA的3 '非翻译区中的特定序列调节 将测定周转率，并且与这些多肽相互作用的多肽 序列将被识别。 最后，将确定是否增强 TopoII mRNA的稳定性增加了相应的蛋白质水平， 导致G2过境点改变

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.