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首页> 外文期刊>Signal transduction: Receptors, mediators and genes: Official journal of the Signal Transduction Society >B lymphocyte-induced maturation protein-1 (Blimp-1) is sufficient to trigger an unfolded protein response and XBP-1 processing in B cells
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B lymphocyte-induced maturation protein-1 (Blimp-1) is sufficient to trigger an unfolded protein response and XBP-1 processing in B cells

机译:B淋巴细胞诱导的成熟蛋白1(Blimp-1)足以触发B细胞中未折叠的蛋白反应和XBP-1加工

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摘要

Terminal differentiation of B cells into antibody secreting plasma cells is an essential step for eliciting a successful humoral immune response. The two transcription factors B lymphocyte-induced maturation protein-1 (Blimp-1) and X-box-binding protein-1 (XBP-1) are indispensable for this process. Hereby, XBP-1 activation depends on Blimp-1. However, it is not known if Blimp-1 alone, in the absence of differentiation signals, can induce XBP-1 processing. Here we show that ectopic expression of Blimp-1 is sufficient to induce an unfolded protein response (UPR), as evidenced by the generation of the processed form of XBP-1 and upregulation of the classical UPR target BIP, in both the B cell lymphoma cell line WEHI 231 and in mouse primary splenic B cells. Interestingly, the amino terminal part of Blimp-1 comprising amino acids 1-751 was sufficient to induce the above effects while the carboxy terminal part comprising amino acids 465-856 had no effect. Taken together our results identify Blimp-1 as the upstream molecule, capable of triggering the UPR in B cells resulting in XBP-1 processing, which is an important step during plasma cell generation.
机译:B细胞最终分化为分泌抗体的浆细胞是引发成功的体液免疫反应的重要步骤。两个转录因子B淋巴细胞诱导的成熟蛋白1(Blimp-1)和X-box结合蛋白1(XBP-1)对于此过程是必不可少的。因此,XBP-1激活取决于Blimp-1。但是,尚不清楚在没有分化信号的情况下,仅Blimp-1是否会诱导XBP-1加工。在这里,我们显示,Blimp-1的异位表达足以诱导未折叠的蛋白应答(UPR),这在两个B细胞淋巴瘤中均可通过XBP-1加工形式的生成和经典UPR目标BIP的上调来证明细胞系WEHI 231和小鼠原代脾B细胞。有趣的是,包含氨基酸1-751的Blimp-1的氨基末端部分足以诱导上述作用,而包含氨基酸465-856的羧基末端部分没有作用。综上所述,我们的结果表明Blimp-1是上游分子,能够触发B细胞中的UPR,从而导致XBP-1加工,这是浆细胞生成过程中的重要步骤。

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