Carina Villegas Diversity Supplement

Carina Villegas 多样性补充品

• 批准号: 10814701
• 负责人: Seth Michael Rubin
• 金额: $ 8.83万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10814701
• 关键词: Biochemical; Biological Assay; Cell Cycle; Cell Cycle Regulation; Cell Proliferation; Cell division; Cells; Chromatin; Chromatin Structure; Complex; DNA biosynthesis; Defect; FOXM1 gene; Gene Expression; Genetic Transcription; Growth; Malignant Neoplasms; Mitosis; Molecular; Normal Cell; Pathway interactions; Phosphorylation; Phosphotransferases; Process; Proteins; Regulation; Research; Structure; Transcriptional Regulation; Work; cancer cell; carina; cell growth; improved; inhibitor; innovation; insight; neoplastic cell; structural biology; transcription factor

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.

项目概要 我们的研究重点是控制细胞生长和分裂周期的机制。这 调节分裂决定的蛋白质和途径的鉴定导致了治疗的抑制剂 癌症。然而，这些抑制剂的缺点表明，仍然存在许多分子机制 我们不了解细胞周期控制的各个方面，需要进一步研究来创新 改进的疗法。细胞周期由两波基因表达组成，以复制 DNA 和 进行有丝分裂。我们将研究控制该细胞的蛋白质的结构、功能和调节—— 周期依赖性基因表达。这些蛋白质包括转录因子或 TF（例如 E2F、B- Myb、FoxM1），其活性刺激转录，负调节 TF 的蛋白质（例如 Rb、 CycF 和 MuvB 复合体）以及磷酸化和磷酸化的激酶（例如 Cdk、Aurora A 和 Plk1） 调节 TF 活性。我们将使用一种将结构生物学与细胞生物学相结合的综合方法 基于测定法来确定这些蛋白质如何相互作用以及染色质如何控制 转录。这些研究将为细胞周期如何发生提供新的机制见解 控制以及转录因子如何通过影响直接调节基因表达 染色质结构。