A novel mutation in the Nfkb2 gene generates-an NF-κB2 "Super repressor"
A novel mutation in the Nfkb2 gene generates-an NF-κB2 "Super repressor"
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DOI：
10.4049/jimmunol.179.11.7514
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Starr, Robyn
中科院分区：
文献类型：
--
作者：
Tucker, Elena;O'Donnel, Kristy;Starr, Robyn
非规范nf - κ B通路调节多种器官和细胞系的发育和功能。我们培育了携带Nfkb2新突变的小鼠，该突变可以阻止抑制前体p100转化为活性亚基p52。突变小鼠表达一种复杂的表型，在多种组织中都有异常，其谱比携带Nfkb2靶向缺失的小鼠更严重。由于缺乏p52，通过非典型途径的信号通路被切断，导致脾脏结构紊乱和B细胞发育中断。NF-kappa B2的抑制性前体形式与RelA相互作用，阻止RelA二聚体在标准和非标准刺激下的激活，这与p52缺乏相结合，导致淋巴结形成和骨稳态缺陷。这些发现证明了NF-kappa B2在调节RelA激活中的关键作用，并提示NF-kappa B成员在规范和非规范信号通路中的功能重叠。
The noncanonical NF-kappa B pathway regulates the development and function of multiple organs and cell lineages. We have generated mice harboring a novel mutation in Nfkb2 that prevents the processing of the inhibitory precursor, p100, into the active subunit, p52. Mutant mice express a complex phenotype with abnormalities in a variety of tissues, and with a spectrum that is more severe than in mice carrying a targeted deletion of Nfkb2. Signaling through the noncanonical pathway is ablated due to the absence of p52, resulting in disorganized splenic architecture and disrupted B cell development. The inhibitory precursor form of NF-kappa B2 interacts with RelA, preventing activation of RelA dimers in response to both canonical and noncanonical stimuli, which in combination with p52 deficiency, results in defective lymph node formation and bone homeostasis. These findings demonstrate a key role for NF-kappa B2 in the regulation of RelA activation and suggest overlap in the function of NF-kappa B members in canonical and noncanonical pathway signaling.