MALT1 directs B cell receptor-induced canonical nuclear factor-κB signaling selectively to the c-Rel subunit
MALT1 directs B cell receptor-induced canonical nuclear factor-κB signaling selectively to the c-Rel subunit
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DOI：
10.1038/ni1493
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发表时间：
2007-09-01
影响因子：
30.5
通讯作者：
Ruland, Juergen
中科院分区：
文献类型：
--
作者：
Ferch, Uta;zum Bueschenfelde, Christian Meyer;Ruland, Juergen
NF-κ B（Rel）转录因子控制生理和病理免疫细胞功能。支架蛋白Bcl-10和MALT 1将抗原受体信号偶联至经典NF-κ B途径，并且在淋巴瘤发生中是关键的。我们发现Bcl-10和MALT 1对B细胞受体诱导的RelA和c-Rel的激活有不同的调节作用。Bcl-10对于将激酶IKK募集到脂筏中以激活RelA和c-Rel、阻断凋亡和诱导B细胞受体连接后的分裂是必需的。相反，MALT 1参与生存信号传导，但不参与IKK募集或激活，并与RelA诱导和增殖有关。MALT 1选择性地激活c-Rel以控制不同的子程序。我们的研究结果提供了B细胞受体诱导的存活和增殖信号的机制见解，并证明了在经典NF-κ B途径中c-Rel的选择性控制。
NF-kappa B (Rel) transcription factors control physiological and pathological immune cell function. The scaffold proteins Bcl-10 and MALT1 couple antigen-receptor signals to the canonical NF-kappa B pathway and are pivotal in lymphomagenesis. Here we found that Bcl-10 and MALT1 differentially regulated B cell receptor-induced activation of RelA and c-Rel. Bcl-10 was essential for recruitment of the kinase IKK into lipid rafts for the activation of RelA and c-Rel, for blocking apoptosis and for inducing division after B cell receptor ligation. In contrast, MALT1 participated in survival signaling but was not involved in IKK recruitment or activation and was dispensable for RelA induction and proliferation. MALT1 selectively activated c-Rel to control a distinct subprogram. Our results provide mechanistic insights into B cell receptor-induced survival and proliferation signals and demonstrate the selective control of c-Rel in the canonical NF-kappa B pathway.