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

Zwollo b细胞特异性激活蛋白（BSAP）被认为在多种b细胞特异性基因的转录调控中发挥重要作用，包括CD19、CD20、V（前b） IgH、Ca和blk。BSAP由Pax-5基因编码，该基因是同源结构域类转录因子Pax基因家族的成员。本项目将在小鼠脾脏和b细胞系中研究Pax-5基因转录本和蛋白的分子性质。初步结果表明，至少有两种备选剪接产物存在于小鼠b细胞群中。这些基因的存在和结构，以及任何其他可选择性剪接的Pax-5异构体在体内的存在和结构将被研究。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)不同的同工异构体能否与它们的DNA靶点（bsap结合位点）相互作用？4)在b细胞发育过程中什么时候出现不同的同工异构体？5) Pax-5亚型的哪些区域参与了蛋白间的相互作用？这些研究将增加我们对Pax-5在b细胞发育过程中的功能作用的理解，并有助于阐明在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，是免疫反应的重要组成部分。b细胞特异性激活蛋白（BSAP）被认为在几个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，该基因是同源结构域类转录因子Pax基因家族的成员。本项目将对小鼠脾脏和b细胞系中Pax-5基因RNA转录本和蛋白的分子性质进行表征，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细胞发育过程中的功能作用的理解，并有助于阐明在b淋巴细胞发育过程中协调细胞增殖和分化的机制。＊＊＊

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. ***