Hidalgo-Estévez Alicia M, González Esther, Punzón Carmen, Fresno Manuel
Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
J Gen Virol. 2006 Jun;87(Pt 6):1603-1612. doi: 10.1099/vir.0.81637-0.
Human immunodeficiency virus type 1 (HIV-1) Tat affects cellular gene expression through modulation of the activity of different transcription factors. Here, the role of Tat in the cooperation between nuclear factor of activated T cells (NFAT) and activator protein 1 (AP-1) transcription factors was investigated. Constitutive or transient Tat expression in Jurkat T cells enhanced cooperative NFAT/AP-1- but not AP-1-dependent transcription independent of its ability to transactivate the HIV-1 LTR. The enhancing effect of Tat took place after nuclear translocation of NFAT. Furthermore, transactivation of an NFAT/AP-1 reporter by transfection of NFAT and c-Jun was strongly enhanced by simultaneous Tat transfection. Moreover, intracellular Tat expression increased the binding of NFAT/AP-1 complexes to the interleukin 2 promoter without significantly altering NFAT- and AP-1-independent binding. HIV-1 Tat interacted with NFAT but not c-Jun. These results indicate that Tat interacts with NFAT, affecting its cooperation with AP-1, without altering independent binding of these transcription factors to DNA.
1型人类免疫缺陷病毒（HIV-1）的反式激活因子（Tat）通过调节不同转录因子的活性来影响细胞基因表达。在此，研究了Tat在活化T细胞核因子（NFAT）与活化蛋白1（AP-1）转录因子之间的协同作用中的作用。Jurkat T细胞中组成型或瞬时Tat表达增强了NFAT/AP-1的协同作用，但不增强AP-1依赖性转录，这与其反式激活HIV-1长末端重复序列（LTR）的能力无关。Tat的增强作用发生在NFAT核转位之后。此外，通过同时转染Tat，转染NFAT和c-Jun对NFAT/AP-1报告基因的反式激活作用得到显著增强。此外，细胞内Tat表达增加了NFAT/AP-1复合物与白细胞介素2启动子的结合，而没有显著改变NFAT和AP-1非依赖性结合。HIV-1 Tat与NFAT相互作用，但不与c-Jun相互作用。这些结果表明，Tat与NFAT相互作用，影响其与AP-1 的协同作用，而不改变这些转录因子与DNA的独立结合
