RUI: Structure and Function of an Alternatively Spliced, B-Cell-Specific, Transcription Factor, PAX-5

RUI：选择性剪接的 B 细胞特异性转录因子 PAX-5 的结构和功能

• 批准号: 9419067
• 负责人: Patty Zwollo
• 金额: $ 24.3万
• 依托单位: Occidental College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-15 至 1997-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9419067&HistoricalAwards=false
• 关键词: RUI; Structure; Function; Alternatively; Spliced

94109067 Zwollo B-cell-specific activating protein (BSAP) is thought to play important roles in the transcriptional regulation of several B-cell-specific genes, including (CD19, CD20, V(pre-B) IgH, Ca, and blk.) BSAP is encoded by the Pax-5 gene, a member of the Pax gene family of homeodomain class transcription factors. In this project, the molecular nature of Pax-5 gene transcripts and proteins will be investigated in mouse spleen and B-cell lines. Preliminary results have revealed that at least two alternative splicing products are present within the murine B-cell population. The presence and structure of those, and any additional alternatively spliced Pax-5 isoforms in vivo will be investigated. To study the structure/function relationships of the different Pax-5 isoforms, the following basic questions will be addressed: 1) What is the structure of the different isoforms? 2) How do the different isoforms effect in vivo transcription? 3) Can the different isoforms interact with their DNA target, the BSAP-binding site? 4) When are the different isoforms present during B-cell development ? 5) Which areas on the Pax-5 isoforms are involved in protein-protein interactions? These studies will increase our understanding of the functional roles that Pax-5 plays during B-cell development, as well as contribute to the elucidation of the mechanisms coordinating cell proliferation and differentiation throughout B-lymphocyte development. %%% B-lymphocytes or B-cells are responsible for producing circulating antibodies in response to antigen stimulation and are an essential component of the immune response. B-cell-specific activating protein (BSAP) is thought to play important roles in the transcriptional regulation of several B-cell-specific genes. BSAP is encoded by the Pax-5 gene, a member of the Pax gene family of homeodomain class transcription factors. In this project, the molecular nature of Pax-5 gene RNA transcripts and proteins will be characterized in mouse spleen and B-cell lines, and the structure/function relationships of the different Pax-5 gene products will be determined. These studies will increase our understanding of the functional roles that Pax-5 plays during B-cell development, as well as contribute to the elucidation of the mechanisms coordinating cell proliferation and differentiation throughout B-lymphocyte development. ***

Zwollo B细胞特异性激活蛋白（BSAP）被认为在几种B细胞特异性基因的转录调节中起重要作用，包括（CD 19、CD 20、V（pre-B）IgH、Ca和blk）。 BSAP由Pax-5基因编码，Pax-5基因是同源结构域类转录因子的Pax基因家族的成员。 在这个项目中，Pax-5基因转录本和蛋白质的分子性质将在小鼠脾脏和B细胞系中进行研究。 初步结果表明，至少有两个选择性剪接产物存在于小鼠B细胞群。 将研究这些以及任何其他可变剪接的Pax-5同种型在体内的存在和结构。 为了研究不同Pax-5异构体的结构/功能关系，将解决以下基本问题：1）不同异构体的结构是什么？ 2)不同的异构体如何影响体内转录？ 3)不同的异构体能与它们的DNA靶点BSAP结合位点相互作用吗？ 4)B细胞发育过程中什么时候出现不同的亚型？ 5)Pax-5亚型上的哪些区域参与蛋白质-蛋白质相互作用？ 这些研究将增加我们对Pax-5在B细胞发育过程中发挥的功能作用的理解，并有助于阐明在整个B淋巴细胞发育过程中协调细胞增殖和分化的机制。 % B淋巴细胞或B细胞负责在抗原刺激下产生循环抗体，是免疫应答的重要组成部分。B细胞特异性激活蛋白（BSAP）被认为在B细胞特异性基因的转录调控中起重要作用。 BSAP由Pax-5基因编码，Pax-5基因是同源结构域类转录因子的Pax基因家族的成员。 在这个项目中，Pax-5基因RNA转录物和蛋白质的分子性质将在小鼠脾脏和B细胞系中进行表征，并确定不同Pax-5基因产物的结构/功能关系。这些研究将增加我们对Pax-5在B细胞发育过程中发挥的功能作用的理解，并有助于阐明在整个B淋巴细胞发育过程中协调细胞增殖和分化的机制。 ***