Mauxion F, Jamieson C, Yoshida M, Arai K, Sen R
Rosenstiel Research Center, Brandeis University, Waltham, MA 02254-9110.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2141-5. doi: 10.1073/pnas.88.6.2141.
The kappa B sequence (GGGACTTTCC) binds a factor, NF-kappa B, that is constitutively found in its functional, DNA binding form only in B lymphocytes. A factor with apparently indistinguishable sequence specificity can be induced in many other cell types, where it is used to regulate inducible gene expression. For example, kappa B-related sequences have been shown to be important for the transcription of a few inducible genes, such as the interleukin 2 receptor alpha-chain gene and the beta-interferon gene. However, these genes are not constitutively active in B lymphocytes, suggesting that other regulatory mechanisms must play a role in determining the patterns of expression. We have investigated the constitutive and inducible transcriptional activity mediated by five kappa B-related sequence elements in two different cell types. We show that in S194 plasma cells the activity of each element correlates well with the relative affinity of B-cell-derived NF-kappa B for that element. This leads to significantly lower transcription enhancement by sites derived from the interleukin 2 receptor or T-cell receptor genes in S194 cells. However, in either EL-4 (T) cells or S194 cells, both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I, showing that NF-kappa B activity can be modulated even in a B-cell line that constitutively expresses this factor.
κB序列(GGGACTTTCC)结合一种因子,即核因子κB(NF-κB),该因子仅在B淋巴细胞中以其功能性DNA结合形式组成性存在。在许多其他细胞类型中可诱导出一种序列特异性明显无法区分的因子,它用于调节可诱导基因的表达。例如,已表明κB相关序列对一些可诱导基因的转录很重要,如白细胞介素2受体α链基因和β干扰素基因。然而,这些基因在B淋巴细胞中并非组成性活跃,这表明其他调节机制必定在决定表达模式中发挥作用。我们研究了由两种不同细胞类型中的五个κB相关序列元件介导的组成性和可诱导转录活性。我们发现,在S194浆细胞中,每个元件的活性与B细胞来源的NF-κB对该元件的相对亲和力密切相关。这导致S194细胞中源自白细胞介素2受体或T细胞受体基因的位点的转录增强明显较低。然而,在EL-4(T)细胞或S194细胞中,两种低亲和力位点均可被I型人类T细胞白血病病毒的tax基因产物显著诱导,这表明即使在组成性表达该因子的B细胞系中,NF-κB活性也可被调节。