THE FAMILY OF KAPPAB REGULATORS FOR GENES IN THE IMMUNE RESPONSE

几种淋巴因子及其他分子的基因调控 参与的免疫反应依赖于一个称为kappaB的10个碱基对的DNA序列。 这个序列结合了一个不断增长的核蛋白家族，这些蛋白能够 严格控制这些基因的转录。重要的是，kappaB 序列是在人类免疫缺陷病毒(HIV)中发现的。红衣主教 KappaB序列的特征是它允许高度转录 在特定的特定情况下，以适当的细胞类型进行时间上的调节 基因。我们正试图阐明这一特定规则是如何发生的。 我们已经在IL-2受体α中发现了kappaB序列附近的序列 链基因调节其活性。它们允许它对 转录因子NK-kappaB仅见于T细胞。此外，我们一直在 使用由Ghosh博士开发的计算机程序 国家生物技术信息中心(国家图书馆 医学)研究含有kappaB的基因启动子之间的关系 破译DNA中编码的协同调节信号的序列。 我们还发现kappaB之间DNA序列的微观异质性 网站具有监管意义。我们发现了一种新的原子核 称为NF-CyT1的因子，优先与KappaB位点相互作用 白介素2基因。NF-CyT1在多种不同组织中的表达 肿瘤生物学条件与IL-2基因表达呈负相关 T细胞。这表明，它可能是一个负面监管机构。非常重要的是， 该因子与HIV的增强子区域结合。我们推测它可能有一个 抑制静息T细胞中HIV病毒转录的作用。

Regulation of genes for several lymphokines as well as other molecules involved immune response depend on a 10 bp DNA sequence termed, kappaB. This sequence binds a growing family of nuclear proteins that are capable of tightly governing transcription of these genes. Importantly, the kappaB sequence is found in the human immunodeficiency virus (HIV). A cardinal feature of the kappaB sequence is that it permits transcription in a highly regulated fashion-temporally and in appropriate cell-types for specific genes. We are attempting to elucidate how this specific regulation occurs. We have found sequences near the kappaB sequence in the IL-2 receptor alpha chain genes modulate its activity. They allow it to respond to the transcription factor NK-kappaB only in T cells. In addition, we have been using a computer program developed by Dr. Ghosh in conjunction with the National Center for Biotechnology Information (National Library of Medicine) to study relationships between gene promoters that contain kappaB sequences to decipher the co-regulatory signals encoded in the DNA. We have also found that the microheterogeneity in DNA sequence among kappaB sites has regulatory significance. We have discovered a novel nuclear factor, termed NF-CYT1 that interacts preferentially with a kappaB site in the interleukin-2 gene. The presence of NF-CYT1 in a number of different biological conditions is inversely correlated with IL-2 gene expression in T cells. This suggests it may be a negative regulator. Very significantly, this factor binds to the enhancer region of HIV. We postulate it may have a role in suppressing HIV viral transcription in resting T cells.