CREB/ATF PROTEINS, GROWTH AND DIFFERENTIATION

信号转导通路最终汇聚在 转录激活以产生特定的基因表达模式 对环境刺激的反应。转录的启动 通过这些信号通路的调节受坐标的调节 结合特定转录因子的表达和/或激活 到基因的控制区。对机制的具体见解 潜在的转录激活最近出现在对 这些转录因子的结构和功能。CREB/ATF 转录反式激活蛋白家族直到最近才被 发现并似乎提供了基因调控之间的联系 对细胞信号通路激活物的反应和表达 病毒反式激活蛋白对基因表达的调节。在……里面 在本申请中，我们建议确定CREB的角色(S)和 ATF-2在生长分化过程中的作用 这些蛋白质的结构性活性和显性负性版本 对FRTL-5细胞生长及L6E9分化的影响 细胞。这一策略的使用消除了调查角色的需要 这个蛋白质大家族中的每一个成员 转录事件由序列特异性的共同机制决定 与Cre调控基序相结合。拟研究的模型系统包括 之所以选择，是因为它们表现出明确的表型变化，以响应 细胞内cAMP水平升高。了解自然和 这些蛋白质在生长机制中作用的重要性(S) 而正常细胞的分化将对 在肿瘤发生过程中对这些过程的理解。

Signal transduction pathways converge ultimately at the level of transcriptional activation to produce specific patterns of gene expression in response to environmental stimuli. The initiation of transcription mediated by these signalling pathways is regulated by the coordinate expression and/or activation of specific transcription factors that bind to the control regions of genes. Specific insights into the mechanisms underlying transcriptional activation have recently arisen from studies of the structure and functions of these transcription factors. The CREB/ATF family of transcriptional transactivating proteins has only recently been discovered and appears to provide a link between the regulation of gene expression in response to activators of cellular signalling pathways and the regulation of gene expression by viral transactivating proteins. In the present application we propose to identify the role(s) of CREB and ATF-2 in the processes of growth and differentiation by utilizing constitutively active and dominant negative versions of these proteins to influence the growth of FRTL-5 cells and the differentiation of L6E9 cells. The use of this strategy obviates the need to investigate the role of each member of this large family of proteins that mediate transcriptional events by the common mechanism of sequence-specific binding to the CRE regulatory motif. The model systems to be studied were chosen because they exhibit defined phenotypic changes in response to the elevation of intracellular levels of cAMP. Understanding the nature and importance of the role(s) of these proteins in the mechanisms of growth and differentiation in normal cells will have profound influences on the understanding of these processes during oncogenesis.