INTRACELLULAR THIOLS REGULATE ACTIVATION OF NUCLEAR FACTOR KAPPA-B AND TRANSCRIPTION OF HUMAN-IMMUNODEFICIENCY-VIRUS
INTRACELLULAR THIOLS REGULATE ACTIVATION OF NUCLEAR FACTOR KAPPA-B AND TRANSCRIPTION OF HUMAN-IMMUNODEFICIENCY-VIRUS
复制标题
DOI：
10.1073/pnas.87.24.9943
复制
发表时间：
1990-12-01
影响因子：
11.1
通讯作者：
HERZENBERG, LA
中科院分区：
文献类型：
--
作者：
STAAL, FJT;ROEDERER, M;HERZENBERG, LA
核因子κB (NF-κB)的激活与多种基因的转录调节有关，并且已被证明对于受人类免疫缺陷病毒(HIV LTR)长末端重复序列控制的基因的表达是必需的。我们在这里表明，细胞内硫醇水平在调节这一过程中发挥着关键作用。即，用肿瘤坏死因子α刺激。和/或佛波醇12-肉豆蔻酸酯13-乙酸酯激活NF-κ.B并显着减少细胞内硫醇； N-乙酰基-L-半胱氨酸是一种有效的硫醇来源，可防止硫醇减少并阻断 NF-.kappa.B 的激活；缺乏激活的 NF-.kappa.B 会阻碍 HIV LTR 的激活及其控制下的基因转录。这些发现揭示了一种以前未被认识的遗传调控机制，其中细胞因子诱导的细胞内硫醇水平的变化对于控制 NF-κB 活性至关重要，从而影响细胞因子刺激的细胞表达的基因谱。
The activation of nuclear factor .kappa.B (NF-.kappa.B) has been implicated in the regulation of transcription of a variety of genes and has been shown to be essential for the expression of genes controlled by the long terminal repeat of human immunodeficiency virus (HIV LTR). We show here that intracellular thiol levels play a key role in regulating this process. That is, stimulation with tumor necrosis factor .alpha. and/or phorbol 12-myristate 13-acetate activates NF-.kappa.B and markedly decreases intracellular thiols; N-acetyl-L-cysteine, an efficient thiol source, prevents that thiol decrease and blocks the activation of NF-.kappa.B; and the lack of activated NF-.kappa.B prevents the activation of the HIV LTR and the transcription of genes under its control. These findings reveal a previously unrecognized genetic regulatory mechanism in which cytokine-induced shifts in intracellular thiol levels are crucial in the control of NF-.kappa.B activity and thereby influence the spectrum of genes expressed by cytokine-stimulated cells.