Overproduction of NFKB2 (lyt-10) and c-Rel: a mechanism for HTLV-I Tax-mediated trans-activation via the NF-kappa B signalling pathway.
Overproduction of NFKB2 (lyt-10) and c-Rel: a mechanism for HTLV-I Tax-mediated trans-activation via the NF-kappa B signalling pathway.
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发表时间：
1994-03
期刊：
影响因子：
8
通讯作者：
J. Lanoix;J. Lacoste;N. Pépin;N. Rice;J. Hiscott
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作者：
J. Lanoix;J. Lacoste;N. Pépin;N. Rice;J. Hiscott
分子、生化和流行病学证据表明HTLV-I是成人T细胞白血病（ATL）的病原体。HTLV-I的Tax蛋白是HTLV-I基因表达的正转录激活因子，是一种病毒致癌基因，其也增加包括GM-CSF、IL-2 R α和IL-2在内的细胞基因的转录。Tax的反式激活作用的细胞靶点之一是转录因子的NF-κ B/Rel家族，免疫调节、细胞因子和病毒基因表达的多效性调节因子。在这份报告中，我们证明了NF κ B 2（lyt-10）和c-Rel在HTLV-1感染和Tax表达细胞中过表达，并共同解释了PMA刺激前后这些细胞中组成性NF-κ B结合活性的大部分。最重要的是，我们发现NF-κ B 2（p100）的表达与DNA结合NF-κ B 2（p52）形式的加工、c-Rel的诱导和NF-κ B介导的基因表达的反式激活之间存在Tax依赖性相关性。此外，NFKB 2前体在HTLV-1感染的细胞中与c-Rel和Tax物理相关。我们提出，NF κ B 2的合成和加工允许连续的核表达，否则细胞质蛋白，并与c-Rel的过表达，NF κ B 2改变NF-κ B B信号通路，并有助于T细胞的白血病转化HTLV-Ⅰ。
Molecular, biochemical and epidemiological evidence implicate HTLV-I as an etiologic agent of adult T cell leukemia (ATL). The Tax protein of HTLV-I, a positive transcriptional activator of HTLV-I gene expression, is a viral oncogene that also increases transcription of cellular genes including GM-CSF, IL-2R alpha and IL-2. One of the cellular targets of the trans-activating effects of Tax is the NF-kappa B/Rel family of transcription factors, pleiotropic regulators of immunoregulatory, cytokine and viral gene expression. In this report, we demonstrate that NFKB2 (lyt-10) and c-Rel are overexpressed in HTLV-I infected and Tax-expressing cells and, together, account for the majority of the constitutive NF-kappa B binding activity in these cells before and after PMA stimulation. Most importantly, we show a Tax-dependent correlation between expression of NFKB2(p100) and processing to the DNA binding NFKB2(p52) form, induction of c-Rel, and trans-activation of NF-kappa B-mediated gene expression. Furthermore, the NFKB2 precursor is physically associated with c-Rel and with Tax in HTLV-I infected cells. We propose that NFKB2 synthesis and processing allows continuous nuclear expression of an otherwise cytoplasmic protein and, in conjunction with overexpression of c-Rel, NFKB2 alters the NF-kappa B signalling pathway and contributes to leukemic transformation of T cells by HTLV-I.