Redox Regulation of the Transcription Factor Pax-5.

转录因子 Pax-5 的氧化还原调节。

• 批准号: 0343606
• 负责人: Patty Zwollo
• 金额: $ 5万
• 依托单位: College of William and Mary
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2005-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0343606&HistoricalAwards=false
• 关键词: Redox; Regulation; Transcription; Factor; Pax

B cells play key roles in the immune response, as they are capable of producing and secreting large amounts of antibodies specific to foreign invaders. The B cell-specific transcription factor Pax-5a plays essential roles during B cell development, cell proliferation, and activation. The Pax-5 gene produces a total of four different protein isoforms: Pax-5a, 5b, 5d, and 5e. Previous work shows that the Pax-5e protein can increase the activity of Pax-5a protein. To investigate the function of Pax-5e in vivo, transgenic mice have been generated which overexpress the Pax-5e protein in B cells. Preliminary data show that such mice have increased numbers of precursor B cells in their bone marrow, while the number of mature B cells of such mice in the spleen is abnormally low. Furthermore, B cells of these transgenic mice show spontaneous cell proliferation in primary cell cultures. This project explores mechanisms that change the cell growth characteristics of B cells and their precursors in Pax-5e-overexpressing mice, focusing on bone marrow and spleen B cells. The intellectual merit of this project includes an increased understanding of the role of Pax-5e in B cell growth. This work is expected to increase knowledge concerning activity of transcription factors that regulate the antibody response. Results will provide new insight into the molecular pathways that lead to normal B cell proliferation as well as elucidate possible causes of malignant B cell growth. Broader impacts of this research include the exposure and research training that will be provided to the students of The College of William and Mary. As the William and Mary biology department has no Ph.D. program, research effort and productivity is entirely based on work by undergraduates and Master's students supervised by their PI. Students have the opportunity to become independent researchers and may be co-authors on papers. The research will also be discussed during seminar courses, exposing "non-research" students to molecular immunology research. In addition, the research will be presented annually at a local elementary school as part of a career program ("Science is women's work") aimed to increase science interest in girls.

B细胞在免疫反应中起着关键作用，因为它们能够产生和分泌大量针对外来入侵者的抗体。B细胞特异性转录因子Pax-5a在B细胞发育、细胞增殖和激活过程中发挥重要作用。Pax-5基因总共产生四种不同的蛋白质亚型：Pax-5a、5b、5d和5e。以往的工作表明，Pax-5e蛋白可以提高Pax-5a蛋白的活性。为了研究Pax-5e在体内的功能，我们建立了在B细胞中过表达Pax-5e蛋白的转基因小鼠。初步数据显示，这些小鼠骨髓中的前体B细胞数量增加，而脾中这些小鼠的成熟B细胞数量异常低。此外，这些转基因小鼠的B细胞在原代细胞培养中显示出自发的细胞增殖。该项目探索了在Pax-5e过度表达的小鼠中改变B细胞及其前体细胞生长特性的机制，重点是骨髓和脾B细胞。这个项目的智力价值包括增加了对Pax-5E在B细胞生长中的作用的理解。这项工作有望增加对调节抗体反应的转录因子活性的了解。这些结果将为了解导致正常B细胞增殖的分子途径以及阐明恶性B细胞生长的可能原因提供新的见解。这项研究的更广泛影响包括将为威廉与玛丽学院的学生提供的接触和研究培训。由于威廉和玛丽生物系没有博士项目，研究努力和生产力完全基于本科生和硕士学生在他们的PI的指导下所做的工作。学生有机会成为独立的研究人员，并可能成为论文的共同作者。这项研究也将在研讨会课程中讨论，让“非研究型”学生接触分子免疫学研究。此外，这项研究将每年在当地一所小学作为职业计划(“科学是妇女的工作”)的一部分，旨在提高对女孩的科学兴趣。