MECHANISM OF REGULATION OF HEAT SHOCK GENE EXPRESSION

典型热休克蛋白(HSP)基因转录增强 强烈地受到热源和其他压力源的影响，在某些情况下， 发展的各个阶段。热休克蛋白被发现参与基础生物学 机制，也被联系到免疫过程和 病理情况，调动医务人员的浓厚兴趣 社区。因此，更好地了解这些属性是很重要的 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，一种包含三个 亮氨酸拉链(LZ)和哺乳动物细胞中的C-末端同源物 区域(CTR)。在非应激的人体细胞中，H2SF1存在于疾病- 已定义的、不能与DNA结合的非活性形式。应激时HSF1 同源三聚，获得DNA结合和转录能力。热度 和其他应激条件导致未折叠的堆积 可能作为触发HSF激活的共同信号的蛋白质。 其中一个热休克蛋白，很可能是一种热休克蛋白70类型的蛋白质，感觉到 应激，并可能直接或间接地负向调节HSF的活性。 建议继续对人类HSF1进行研究，以1)测试 假设三聚化是控制的主要监管事件 HSF1的DNA结合能力、核转运和转录活性 并证明了在非应激细胞中通过以下方式防止了三聚化 涉及三个LZ和CTR的蛋白质-蛋白质相互作用 区域，2)提供证据，证明三聚化的监管是基于 HSP70与后几个基序的可逆相互作用，3)检验 磷酸化是否在HSF1的激活和4)研究中起作用 HSF1在体外应激后失活的过程。果蝇Hsp27 23个基因在三龄后期幼虫中表达活跃，并受 蜕皮激素受体(ECR)。Hsp27基因表现为初级基因，而 Hsp23基因作为次级激素反应基因。这一差异 调控是通过ECR在启动子中的结合位点而介导的 这两个基因可以作为早晚基因研究的新范式。 果蝇幼虫的调控。我们建议尝试澄清 这种不同监管背后的机制。

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.