CREB/ATF PROTEINS, GROWTH AND DIFFERENTIATION

信号转导途径最终会聚在 转录激活产生特定的基因表达模式 对环境刺激的反应。转录起始 由这些信号传导途径介导的是由协调调节 特异性转录因子的表达和/或激活，所述转录因子结合 基因的控制区域。 对机制的具体见解 潜在的转录激活最近出现的研究， 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。 发现并似乎提供了基因调控之间的联系， 响应于细胞信号传导途径的活化剂的表达， 病毒反式激活蛋白对基因表达的调节。 在 在本申请中，我们提出确定CREB的作用， ATF-2在生长和分化过程中的作用 这些蛋白质的组成型活性和显性负性版本， 影响FRTL-5细胞的生长和L 6 E9的分化 细胞使用这种策略避免了调查角色的需要 这个蛋白质大家族的每个成员， 转录事件的共同机制的序列特异性 与CRE调节基序结合。拟研究的模型系统为 之所以选择它们，是因为它们表现出明确的表型变化， 细胞内cAMP水平升高。了解自然和 这些蛋白质在生长机制中的重要性 正常细胞的分化将对细胞的分化产生深远的影响。 了解肿瘤发生过程中的这些过程。

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.