Role of FBXO45 in Diffuse Large B Cell Lymphoma Pathogenesis

项目摘要 FBXO 45在人大B细胞淋巴瘤发病中的作用 弥漫性大B细胞淋巴瘤（DLBCL）是一种侵袭性淋巴瘤，代表了 西半球最常见的恶性淋巴瘤。生物事件 DLBCL的潜在发病机制尚未完全了解。我们最近 鉴定了FBXO 45的功能失活，FBXO 45是DLBCL中的E3泛素连接酶。在这 应用中，我们将利用转基因小鼠模型来探索生物学作用， FBXO 45在B细胞分化和淋巴瘤发生中的作用此外，我们将采用 生物化学和分子生物学技术，以更好地了解FBXO 45在 DLBCL的发病机制。因此，我们在本申请的第一个目的中提出利用 新创建的转基因小鼠模型，以功能性地询问FBXO 45在B- 细胞发育和淋巴瘤发生。在第二个目标中，我们将确定全球 FBXO 45在B细胞环境中的细胞底物。这些研究将确定 FBXO 45在DLBCL发病机制中的作用，并建立其作用机制。 放松管制有助于DLBCL。

PROJECT SUMMARY THE ROLE OF FBXO45 IN DIFFUSE LARGE B-CELL LYMPHOMA PATHOGENESIS Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma and represents the most common form of malignant lymphoma in the western hemisphere. The biologic events underlying the pathogenesis of DLBCL are not completely understood. We have recently identified functional inactivation of FBXO45, an E3 ubiquitin ligase in DLBCL. In this application, we will utilize transgenic mouse models to explore the biological roles for FBXO45 in B-cell differentiation and lymphomagenesis. Further, we will employ biochemical and molecular biology techniques to better understand the role FBXO45 in the pathogenesis of DLBCL. Accordingly, we propose in the first aim of this application to utilize newly created transgenic mouse models to functionally interrogate the role of FBXO45 in B- cell development and lymphomagenesis. In the second aim, we will identify the global cellular substrates of FBXO45 in B cell contexts. These studies will establish the role of FBXO45 in the pathogenesis of DLBCL and establish the mechanisms by which its deregulation contributes to DLBCL.