Molecular Mechanisms of Cell Cycle Dependent Gene Expression

项目总结 我们的研究集中在控制细胞生长和分裂周期的机制上。这个 对调节分裂决定的蛋白质和途径的识别导致了抑制剂的治疗 癌症。然而，这些抑制剂的缺点清楚地表明，仍有许多分子 细胞周期控制的一些我们不了解的方面，还需要进一步的研究来创新 改进治疗方法。细胞周期由两波基因表达组成，以复制DNA和 进行有丝分裂。我们将研究控制这个细胞的蛋白质的结构、功能和调节- 依赖于周期的基因表达。这些蛋白质包括转录因子或转录因子(例如E2F、B- MYB，FOXM1)，其活性刺激转录，负向调节TF的蛋白质(例如，Rb， CycF和MuvB复合体)，以及磷酸化和 调节转铁蛋白活性。我们将使用一种综合的方法，将结构生物学和细胞- 基于分析来确定这些蛋白质如何相互作用以及染色质如何控制 抄写。这些研究将提供关于细胞周期如何的新的机械学见解 转录因子如何通过影响直接调控基因表达 染色质结构。

PROJECT SUMMARY Our research is focused on the mechanisms that control the cell cycle of growth and division. The identification of proteins and pathways that regulate the decision to divide has led to inhibitors to treat cancer. However, the shortcomings of these inhibitors make it clear that there are still many molecular aspects of cell-cycle control that we do not understand, and further research is needed to innovate improved therapies. The cell cycle consists of two waves of gene expression to replicate DNA and undergo mitosis. We will study the structure, function, and regulation of proteins that control this cell- cycle dependent gene expression. These proteins include the transcription factors or TFs (e.g. E2F, B- Myb, FoxM1) whose activity stimulates transcription, proteins that negatively regulate the TFs (e.g. Rb, CycF, and the MuvB complex), and the kinases (e.g. Cdk, Aurora A, and Plk1) that phosphorylate and modulate TF activity. We will use an integrated approach that combines structural biology with cell- based assays to determine how these proteins interact with each other and chromatin to control transcription. These studies will provide new mechanistic insights regarding how the cell cycle is controlled and how transcription factors directly modulate gene expression through influencing chromatin structure.