Role of ubiquitin networks in NF-κB driven B cell neoplasms (P06)

泛素网络在 NF-κB 驱动的 B 细胞肿瘤中的作用 (P06)

• 批准号: 405442817
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin III: Hämatologie und Onkologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405442817?language=en
• 关键词: Role; ubiquitin; networks; NF; driven

Activation of NF-κB is regulated by signalling cascades that depend on protein phosphorylation and activities of the ubiquitin system. We identified the ubiquitin ligases KBTBD7, KLHL21 and FBXO41 as candidates that mediate NF-κB activation in ABC-type DLBCL and found BCMA, an NF-κB activator and target for cellular immunotherapies in multiple myeloma (MM), to be regulated by the ubiquitin proteasome system (UPS). This project will strive to obtain a holistic mechanistic understanding of how ubiquitin ligases sustain NF-κB activity in DLBCL, how the UPS can direct BCMA activity and expression in MM and how these insights can forward novel actionable therapeutic targets.

NF-κB的激活受依赖于蛋白磷酸化和泛素系统活性的信号级联调控。我们确定了泛素连接酶KBTBD7、KLHL21和FBXO41作为介导abc型DLBCL中NF-κB激活的候选酶，并发现BCMA是一种NF-κB激活剂和多发性骨髓瘤（MM）细胞免疫治疗的靶标，受泛素蛋白酶体系统（UPS）的调节。该项目将努力获得泛素连接酶如何在DLBCL中维持NF-κB活性的整体机制理解，UPS如何指导MM中的BCMA活性和表达，以及这些见解如何提出新的可操作的治疗靶点。