NF‐κB‐dependent signals control BOB.1/OBF.1 and Oct2 transcriptional activity in B cells

NF‐κB‐dependent signals control BOB.1/OBF.1 and Oct2 transcriptional activity in B cells
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NFκB 依赖性信号控制 B 细胞中的 BOB 1/OBF 1 和 Oct2 转录活性

DOI:
10.1002/eji.201545475
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发表时间:
2015
影响因子:
5.4
通讯作者:
Brunner
Brunner
中科院分区:
医学3区
文献类型:
--
作者:
Kilzheimer;Quandt;Langhans;Weihrich;Brunner

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转录共激活因子 BOB.1/OBF.1 对于 B 细胞中八聚体驱动的转录至关重要。 BOB.1/OBF.1 缺陷会导致 B 细胞发育和功能的巨大缺陷。因此,过去的研究主要集中在BOB.1/OBF.1靶基因的鉴定上。然而,人们对 BOB.1/OBF.1 表达本身的调节知之甚少。在这里,我们表明,在 B 细胞中,NF-κB 以及在某种程度上 NFAT 蛋白通过直接结合 BOB.1/OBF.1 启动子参与基础以及诱导型 BOB.1/OBF.1 表达的激活。此外,对不同 NF-κB 诱导剂(如几种 TLR 配体、TNF-α、BAFF 或 LTα1β2)的分析表明,经典和非经典 NF-κB 途径均参与 BOB.1/OBF.1 基因的诱导。迄今为止未知的调节 B 细胞中 BOB.1/OBF.1 表达的诱导剂的鉴定为 BOB.1/OBF.1 在 B 细胞发育和功能的不同方面的潜在功能提供了新的见解。
The transcriptional co‐activator BOB.1/OBF.1 is crucial for Octamer‐driven transcription in B cells. BOB.1/OBF.1‐deficiency leads to tremendous defects in B‐cell development and function. Therefore, in the past research focused on the identification of BOB.1/OBF.1 target genes. However, the regulation of BOB.1/OBF.1 expression itself is poorly understood. Here we show that in B cells NF‐κB as well as to some extent NFAT proteins are involved in the activation of basal as well as inducible BOB.1/OBF.1 expression by direct binding to theBOB.1/OBF.1promoter. Moreover, the analysis of different inducers of NF‐κB, like several TLR ligands, TNF‐α, BAFF, or LTα1β2, revealed that both the canonical and noncanonical NF‐κB pathways are involved in the induction ofBOB.1/OBF.1gene. The identification of so far unknown inducers that regulate BOB.1/OBF.1 expression in B cells provides novel insights in the potential function of BOB.1/OBF.1 during different aspects of B‐cell development and function.
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