The analysis of mouse models in order to define the roles of IKK/NF-KappaB and JNK signaling in lymphocyte physiology and pathology

分析小鼠模型以确定 IKK/NF-KappaB 和 JNK 信号在淋巴细胞生理学和病理学中的作用

• 批准号: 35879735
• 负责人: Professor Dr. Marc Schmidt-Supprian
• 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: Independent Junior Research Groups
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/35879735?language=en
• 关键词: analysis; mouse; models; order; define

In order to react to environmental changes, cells transmit information from the cell membrane to the nucleus in order to reprogram gene-expression. IκB Kinase (IKK)- mediated activation of NFκB transcription factors and c-Jun N-terminal Kinase (JNK) signaling are two important signaling pathways that relay information during immune responses. They regulate immune cell development and function, cellular proliferation and cell death. NFκB proteins have been implicated in a variety of hereditary and acquired human diseases and constitutive NFκB activation is a hallmark of various B cell malignancies. Likewise, active JNK has been identified in B lymphomas, suggesting a role for aberrant JNK-activity in lymphomagenesis. My proposal aims at elucidating the roles of IKK and JNK signaling in the context of immunity and tumorigenesis through the generation of genetically modified mice. The consequences of absent or constitutively active signaling will be evaluated at the cellular and biochemical level in vivo. In addition, I will employ novel genetic strategies to identify oncogenic events, that co-operate with constitutive IKK or JNK activation to induce tumorigenesis.

为了应对环境变化，细胞将信息从细胞膜传递到细胞核，以重新编程基因表达。IκB激酶（IKK）介导的NFκB转录因子活化和c-Jun N末端激酶（JNK）信号传导是免疫应答过程中传递信息的两条重要信号传导途径。它们调节免疫细胞的发育和功能、细胞增殖和细胞死亡。NFκB蛋白与多种遗传性和获得性人类疾病有关，组成性NFκB活化是多种B细胞恶性肿瘤的标志。同样，在B淋巴瘤中也发现了活性JNK，提示异常JNK活性在淋巴瘤发生中的作用。我的建议旨在阐明IKK和JNK信号转导的免疫和肿瘤发生的背景下，通过产生转基因小鼠的作用。将在体内的细胞和生化水平上评价不存在或组成型活性信号传导的后果。此外，我将采用新的遗传策略，以确定致癌事件，合作与组成型IKK或JNK激活，以诱导肿瘤发生。

项目成果

A20 and CYLD Do Not Share Significant Overlapping Functions during B Cell Development and Activation

• DOI: 10.4049/jimmunol.1200396
• 发表时间: 2012-11-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Chu, Yuanyuan;Soberon, Valeria;Schmidt-Supprian, Marc
• 通讯作者: Schmidt-Supprian, Marc