POLYADENYLATION FACTORS IN B CELLS, LYMPHOMA AND MYELOMA

B 细胞、淋巴瘤和骨髓瘤中的多腺苷酸化因子

• 批准号: 6044738
• 负责人: Christine Ann Milcarek
• 金额: $ 20.48万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-15 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6044738
• 关键词: B lymphocyte; CD40 molecule; RNA splicing; binding proteins; gene induction /repression; heterogeneous nuclear ribonucleoprotein; immunoglobulin genes; immunoglobulins; immunologic memory; interferon gamma; leukocyte activation /transformation; lipopolysaccharides; lymphoma; macrophage; molecular cloning; multiple myeloma; nuclear factor kappa beta; plasma cells; polyadenylate; tissue /cell culture

DESCRIPTION: (Adapted from the Investigator's abstract) The cleavage and polyadenylation reaction has been shown to play an important role in modulating Ig heavy chain poly(A) site use in B-cell development. This application focuses on defining the mechanisms of how these changes in the molecular nature, quantity, affinity for RNA, and interactions of CstF-64 (64 kDa subunit of cleavage stimulatory factor of the polyadenylation reaction) with other components of the polyadenylation/cleavage machinery operate and influence poly(A) site choice during the induction of plasma and memory cells. We propose to test the following: Aim 1 Three proteins have been identified by our lab whose amount or activity varies between plasma cells and earlier B-cell stages. We will test the hypothesis that their interactions with CstF-64, CPSF100 or the downstream region of RNA can influence polyadenylation patterns in B-cell stages. Aim 2. Experiments are proposed to address our hypothesis that the changes in CstF-64 binding activity we previously observed are brought about in part by mechanisms intrinsic to the CstF-64 protein. Aim 3. We will to test the hypothesis that CstF-64 up-regulation is mediated by NF-kB in lipopolysaccharide and interferon-gamma stimulation and CD 40 ligand-mediated B-cell growth. The experiments described in this application attempt to find differences in cells that may serve as markers to identify memory, naive, and plasma B-cells as well as to understand the molecular events that determine how memory an/or B-cells may be activated to differentiate into plasma cells. Understanding immunological memory is important for vaccine development to eradicate infectious diseases, mediating allergic responses and autoimmune diseases, and limiting tumor growth. Understanding the control of polyadenylation is important for understanding and possibly controlling many aspects of cell growth, differentiation and malignancy.

描述：（改编自研究者的摘要）裂解和 多聚腺苷酸化反应已被证明在调节中发挥重要作用 B 细胞发育中 Ig 重链 Poly(A) 位点的使用。该应用程序重点 定义分子性质如何变化的机制， CstF-64（CstF-64 的 64 kDa 亚基）的数量、对 RNA 的亲和力以及相互作用 多聚腺苷酸化反应的裂解刺激因子）与其他 多聚腺苷酸化/裂解机器的组成部分的运作和影响 血浆和记忆细胞诱导过程中多聚（A）位点的选择。我们建议 测试以下内容： 目标 1 我们的实验室已鉴定出三种蛋白质 其数量或活性在浆细胞和早期 B 细胞阶段之间有所不同。 我们将检验以下假设：它们与 CstF-64、CPSF100 或 RNA 的下游区域可以影响 B 细胞中的聚腺苷酸化模式 阶段。目标 2. 提出实验来解决我们的假设 我们之前观察到的 CstF-64 结合活性的变化是在 部分是由 CstF-64 蛋白固有的机制决定的。 目标 3. 我们将检验 CstF-64 上调是由以下因素介导的假设： 脂多糖中的 NF-kB 和干扰素-γ 刺激以及 CD 40 配体介导的 B 细胞生长。本申请中描述的实验 尝试寻找可作为识别标记的细胞差异 记忆、幼稚和血浆 B 细胞以及了解分子事件 决定记忆和/或 B 细胞如何被激活以分化为 浆细胞。了解免疫记忆对于疫苗很重要 根除传染病、调节过敏反应和 自身免疫性疾病，并限制肿瘤生长。了解控制 多聚腺苷酸化对于理解和可能控制许多 细胞生长、分化和恶性肿瘤等方面。