PROTEIN INTERACTIONS REGULATING PITUITARY SIGNALING

描述(取自应用程序) 转录活性不仅取决于转录的结合 影响顺式作用元件的因素，也影响这些因素的能力 招募复杂的蛋白质层次结构来稳定基础转录 机械设备。大鼠催乳素(RPRL)基础催乳素的特异性表达 启动子依赖于原癌蛋白c-ets-1，a -Ets转录因子家族的成员，具有脑垂体特异性 转录因子Pit-1在Ets/Pit-1 DNA结合元件上的表达 RPRL启动子。虽然这些因素中的每一个都能够单独激活 RPRL基因转录，这两种转录因子的结合 结果产生了显著的协同反应。尽管精确的控制机制 这种协同作用仍然未知，很明显，这些物质的物理相互作用 有两个因素是必需的。最近的研究表明，Pit-1和Pit-1的活性 Ets-1可能由共调节复合体的形成所决定。因此，我 假设Pit-1/Ets-1复合体介导的协同反应 RPRL启动子通过招募特定的转录调节蛋白。这个 本研究的目标是定位Pit-1和Ets-1的特定氨基酸 负责他们的身体和功能的相互作用，并使用液体 色质联用法鉴定蛋白质组分 被招募到ETS-1/Pit-1复合体的人。因此，这些研究是 可能会对潜在的分子机制提供关键的见解 组合因子相互作用及其如何调节协同反应。 最后，这些学习对我的职业发展很重要，它们将会 请允许我在蛋白质组学和蛋白质的前沿领域获得专业知识 结构-功能关系，然后我可以利用它来建立我的 独立调查员的职业生涯。

DESCRIPTION (taken from the application) Transcriptional activity is dependent not only on the binding of transcription factors to cis-acting elements, but also on the ability of those factors to recruit a complex hierarchy of proteins to stabilize the basal transcriptional machinery. Basal lactotroph specific expression of the rat prolactin (rPRL) promoter is dependent on the interaction of the proto-oncoprotein c-Ets-1, a member of the -Ets family of transcription factors, with the pituitary-specific transcription factor, Pit-1, at a composite Ets/Pit-1 DNA binding element in the rPRL promoter. While each of these factors alone is capable of activating rPRL gene transcription, the combination of these two transcription factors results in a marked synergistic response. Although the precise mechanism for this synergy remains unknown, it is clear that physical interaction of these two factors is required. Recent studies suggest that the activity of Pit-1 and Ets-1 may be determined by the formation of co-regulatory complexes. Thus, I hypothesize that the Pit-1/Ets-1 complex mediates the synergistic response of the rPRL promoter by recruiting specific transcription regulatory proteins. The goals of this study are to map the specific amino acids of Pit-1 and Ets-1 responsible for their physical and functional interaction, and to use liquid chromatography/mass spectrometry methods to identify the protein components that are recruited to the Ets-1/Pit-1 complex. Therefore, these studies are likely to provide critical insights into the molecular mechanisms underlying combinatorial factor interactions and how they mediate synergistic responses. Finally, these studies are important to my career development, as they will allow me to gain expertise in the cutting edge field of proteomics and protein structure-function relationships, which I can then utilize to establish my career as an independent investigator.