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Role of FBXO45 in Diffuse Large B Cell Lymphoma Pathogenesis

FBXO45 在弥漫性大 B 细胞淋巴瘤发病机制中的作用

基本信息

批准号：
10412096
负责人：
KOJO S. J. ELENITOBA-JOHNSON
金额：
$ 2.49万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-03 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10412096
关键词：
3q29 Affinity Affinity Chromatography B cell differentiation B-Cell Development B-Cell Lymphomas B-Lymphocyte Subsets B-Lymphocytes BCL2 gene BCL6 gene Biochemical Biological Biological Process Birth Cancer Etiology Cell Differentiation process Cell Line Cell physiology Cells Cellular biology Cessation of life Characteristics Clustered Regularly Interspaced Short Palindromic Repeats Communities Complement Constitutional Cullin Proteins Data Development Event F Box Domain Family Gene Targeting Genes Genetic Genomics Growth Guanine Nucleotide Exchange Factors Hour Human Knock-in Knock-out Lymphoma Lymphomagenesis MS4A1 gene Malignant Neoplasms Mediating Molecular Molecular Biology Techniques Mus Mutagenesis Neoplasms Oncogenic Pathogenesis Pharmacology Play Proteolysis Proteomics RNA RNA Interference Recurrence Research Resources Role Sampling Structure of germinal center of lymph node Tamoxifen Testing Time Transgenic Mice Tumor Suppressor Genes Tumor Suppressor Proteins Tumorigenicity Ubiquitin-mediated Proteolysis Pathway Update Xenograft Model cohort genome sequencing in vivo insight large cell Diffuse non-Hodgkin&apos s lymphoma member mouse model novel novel therapeutic intervention prognostic proteogenomics screening small hairpin RNA tandem mass spectrometry targeted treatment treatment strategy ubiquitin ligase ubiquitin-protein ligase whole genome

项目摘要

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.

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。