GENE ACTIVATION BY POLYPEPTIDES--CELL SURFACE TO NUCLEUS

胚胎发育过程中的许多发育事件和成人的调节事件取决于 细胞外信号多肽(ESP)的存在。超过35个不同的ESP立即使用他们的 通过激活一组称为STATS的潜在转录因子发挥作用，STAT是一种双功能蛋白 作为sjgnal转导和转录激活子。一系列生理事件 至少部分由统计数据控制，包括先天免疫，即对入侵的初始反应 细菌和病毒，适当的T细胞功能，特别是在选择免疫反应的类型 入侵的生物体和骨髓中的许多其他功能。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的正确反应也取决于 这些蛋白质。最后，适当的生长控制需要这些蛋白质的作用。这个项目有 主要的长期目标是了解统计数据的核作用的分子基础。 改变转录速率。我们将完成之前关于转录的定义的研究 通过体内转录和细胞生物学检测Stats 1、Stats 2和Stats 3的激活域TADS 分析每种TAD的特异性。与-COOH末端特异相互作用的蛋白质 TAD的STATL，一个已经被证明是转录激活所必需的结构域 检测到。这些TAD相互作用蛋白的质谱学鉴定 通过多肽含量或克隆以前未被识别的蛋白质的基因来鉴定将是一个主要的 最初的目标。这些相互作用的蛋白质很可能包括共激活因子，它们可能是 STAT组转录因子在体内和体外转录检测中的作用 然后将进行失速-TAD相互作用蛋白。态的功能相互作用研究 1、2和3相互作用的蛋白质应该提供对STAT蛋白质如何变化的全面洞察 基因转录诱导或维持与许多相关的特定表型特性 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 sjgnal 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 Statl, 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 Stall-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.