MECHANISM OF REGULATION OF HEAT SHOCK GENE EXPRESSION

典型的热休克蛋白（HSP）基因的转录增强 在某些情况下，热和其他压力因素， 发展阶段 Hsps被发现参与基本的生物学过程， 机制，也与免疫过程有关， 病理条件，调动强烈的兴趣，由医疗 社区 因此，更好地理解这些特性是很重要的。 热休克蛋白及其表达的调控。 压力调节是 由热休克转录因子HSF介导，HSF是一种含有三个 亮氨酸拉链（LZ），在哺乳动物细胞中，C-末端同源 区域（CTR）。 在未应激的人类细胞中，H2SF 1存在于一个病态的细胞中。 不能与DNA结合的确定的、不活跃的形式。 应激后HSF 1 同源三聚化，获得DNA结合和转录能力。 热 和其他压力条件导致非折叠的 可能作为触发HSF激活的共同信号的蛋白质。 其中一种热休克蛋白，很可能是一种热休克蛋白70型蛋白， 应激，并可直接或间接地负调节HSF活性。 建议继续使用人HSF 1进行研究，以1）测试 假设三聚化是控制细胞凋亡的主要调控事件， hSF 1的DNA结合能力、核转运和转录活性 并证明在未应激的细胞中， 涉及所有三个LZ以及CTR的蛋白质-蛋白质相互作用 区域，2）提供证据表明，三聚化的调节是基于 热休克蛋白70与后者的一些基序的可逆相互作用，3）检查 磷酸化是否在HSF 1、活化中起作用，以及4）研究 体外观察应激后HSF 1的失活过程。 果蝇热休克蛋白27 和23个基因在三龄后期幼虫中是活跃的，并且由 蜕皮甾酮受体（EcR）。 热休克蛋白27基因的行为作为一个主要的，和 hsp 23基因作为次级应答基因。 此差分 调节是通过在启动子中的EcR结合位点介导的， 这两个基因，并可能作为一个新的范式研究早期与晚期基因 调节果蝇幼虫。 我们建议尝试澄清 这种差异调节的机制。

Transcription of typical heat shock protein (hsp) genes is enhanced drastically be heat and other stressors, and, in some cases, at distinct stages of development. Hsps are found to participate in basic biological mechanisms and have also been linked to immunological processes and pathological conditions, mobilizing intense interest by the medical community. It is therefore important to better understand the properties of hsps and the regulation of their expression. Stress regulation is mediated by heat shock transcription factor HSF, a protein containing three leucine zippers (LZs) and , in mammalian cells, a C-terminal homology region (CTR). In unstressed human cells, H2SF1 is present in an ill- defined, inactive form incapable of DNA binding. Upon stress HSF1 homotrimerizes, acquiring DNA binding and transcriptional ability. Heat and other stressful conditions result in the accumulation of nonfolded proteins that may serve as the common signal triggering HSF activation. One of the hsps, most likely an hsp70-type protein, senses the level of stress and may, directly or indirectly, negatively regulate HSF activity. Continuation of studies with human HSF1 is proposed to 1) test the hypothesis that trimerization is the master regulatory event that controls DNA binding ability, nuclear transport and transcriptional activity of hSF1 and demonstrate that trimerization is prevented in unstressed cells by protein-protein interactions involving all three LZs as well as the CTR region, 2) provide evidence that regulation of trimerization is based on reversible interactions of hsp70 with some of the latter motifs, 3) examine whether phosphorylation plays a role in HSF1, activation, and 4) study in vitro the process of HSF1 inactivation following stress. Drosophila hsp27 and 23 genes are active in late third instar larvae and are regulated by ecdysterone receptor (EcR). The hsp27 gene behaves as a primary, and the hsp23 gene as a secondary hormone-responsive gene. This Differential regulation is mediated through binding sites for EcR in the promoters of the two genes and may be studied as a novel paradigm for early v. late gene regulation in Drosophila larvae. We propose to attempt the elucidation of the mechanism underlying this differential regulation.