GENE ACTIVATION BY POLYPEPTIDES--CELL SURFACE TO NUCLEUS

超出提供的空间。胚胎发育过程中的许多发育事件和成体的调节事件依赖于细胞外信号多肽(ESPs)的存在。超过35种不同的ESP通过激活一组称为STATS的潜在转录因子发挥直接作用，STATS是作为sjgnal转导和转录激活剂的双功能蛋白。至少部分由统计数据控制的一系列生理事件包括先天免疫，即对入侵细菌和病毒的初始反应，适当的T细胞功能，特别是在选择对入侵生物的免疫反应类型方面，以及骨髓中的许多其他功能。发育事件，如乳腺组织中正常的上皮细胞发育和对生长激素的正确反应，也依赖于这些蛋白质。最后，适当的生长控制需要这些蛋白质的作用。该项目的中心长期目标是了解STATS在改变转录速率时的核作用的分子基础。我们将通过体内转录和细胞生物学检测每个TAD的特异性来完成我们对Stats 1、2和3转录激活结构域(TADS)定义的早期研究。与STATL的-COOH末端TAD特异相互作用的蛋白质已经被检测到，这个区域已经被证明是转录激活所必需的。通过多肽含量的质谱学鉴定或通过克隆以前未被识别的蛋白质的基因来鉴定每一种TAD相互作用的蛋白质将是主要的初始目标。这些相互作用的蛋白质很可能包括在体内和体内针对STAT转录因子组的共激活因子。然后将对这些失速相互作用蛋白的作用进行体外转录分析。对Stat 1、Stat 2和Stat 3相互作用蛋白的功能相互作用的研究应该为STAT蛋白如何改变基因转录以诱导或维持与许多细胞外信号多肽相关的特定表型属性提供全面的见解。表演网站========================================Section End===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================