GENE ACTIVATION BY POLYPEPTIDES--CELL SURFACE TO NUCLEUS

胚胎发育过程中的许多发育事件和调节事件 成体依赖于细胞外信号多肽的存在 (ESP)。超过35个不同的公共服务提供者通过 激活一组称为STATS、DUAL的潜在转录因子 作为信号转导和激活因子的功能蛋白 抄写。生理事件的阵列至少控制在 部分统计数据包括先天免疫力，即对 入侵的细菌和病毒，正常的T细胞功能，特别是在 选择免疫反应的类型，以应对入侵生物和许多 骨髓的其他功能。发展事件，如适当的 乳腺组织中上皮细胞的发育和对 生长激素也依赖于这些蛋白质。最后，适当的成长 控制需要这些蛋白质的作用。这个项目有 中心的长期目标是了解细胞的分子基础 统计数据在改变转录速率时的核作用。我们会 完成我们早期关于转录的定义的研究 体内检测Stats 1、Stats 2和Stats 3的激活域TADS 转录和细胞生物学检测每个TAD的特异性。 与-COOH末端TAD特异相互作用的蛋白质 STAT1中已演示需要的域 已经检测到转录激活。身份的鉴定 通过质谱学分析这些TAD相互作用蛋白中的每一个 通过多肽含量或克隆以前的基因进行鉴定 未被识别的蛋白质将是一个主要的初始目标。这些互动 蛋白质很可能包括共激活因子，它可能是 转录因子STAT组。体内和体外 这些STAT1-TAD相互作用的转录分析 然后，蛋白质将被执行。泛函的研究 Stat 1、Stat 2和Stat 3相互作用的蛋白质应该提供 全面了解STAT蛋白如何改变基因转录 诱导或维持与…有关的特定表型特性 许多胞外信号多肽。

Many developmental events during embryogenesis and regulatory events in adults depend upon the presence of extracellular signalling polypeptides (ESPs). Over 35 different ESPs exert their immediate effect through the activation of a set of latent transcription factors called STATs, dual function proteins that serve as signal transducers and activators of transcription. The array of physiologic events controlled at least in part by the STATs include innate immunity, i.e. the initial response to invading bacteria and viruses, proper T cell function particularly in choosing the type of immune responses to invading organisms and many other functions in the bone marrow. Developmental events such as proper epithelial cell development in breast tissue and correct responses to growth hormone also depend on these proteins. Finally, proper growth control requires the action of these proteins. This project has the central long-term goal of understanding the molecular basis for the nuclear action of the STATs in changing transcription rates. We will complete our earlier studies on the definition of transcriptional activation domains, TADs, of Stats 1, 2 and 3 by testing in in vivo transcriptional and cell biologic assays the specificity of each TAD. Proteins that are specifically interactive with the -COOH terminal TAD of Stat1, a domain already demonstrated to be required in transcriptional activation have been detected. The identification of each of these TAD-interactive proteins through mass spectrographic identification by peptide content or by cloning genes of previously unrecognized proteins will be a major initial goal. These interactive proteins very likely include co-activators that may be specific for the STAT group of transcription factors. In vivo and in vitro transcriptional assays of the role of these Stat1-TAD interactive proteins will then be carried out. The studies of functional interaction of the Stat 1, 2 and 3 interactive proteins should provide comprehensive insight into how STAT proteins change gene transcription to induce or maintain the specific phenotypic properties associated with the many extracellular signalling polypeptides.