NF-kappa B homodimer binding within the HIV-1 initiator region and interactions with TFII-I.

We show that the binding of Rel p50 and p52 homodimers at sites within the transcriptional initiation region of HIV-1 provides for their ability to interact with other proteins that bind the initiator. The binding of one such protein, the initiator protein TFII-I, to the initiation region of HIV-1 is augmented in the presence of Rel p50 and Rel p52 homodimers. Consistent with this, in vitro Rel homodimers potentiate HIV-1 transcription in a manner dependent upon TFII-I. The findings suggest that Rel dimers may regulate HIV-1 transcription in two ways. First, through binding at the kappa B enhancer sites at (-104 to -80), NF-kappa B p50:p65 participates in classical transcriptional activation. Second, Rel dimers such as p50 or p52 might bind at initiator sequences to regulate the de novo binding of components of certain preinitiation complexes. These findings, and the existence of Rel binding sites at the initiators of other genes, suggest roles for Rel proteins in early events determining transcriptional control. IMAGES:

本研究证实，Rel p50与p52同源二聚体（homodimer）结合至人类免疫缺陷病毒1型（HIV-1）转录起始区域（transcriptional initiation region）内的位点后，可获得与结合起始子（initiator）序列的其他蛋白质相互作用的能力。此类蛋白质之一——起始子蛋白TFII-I——与HIV-1转录起始区域的结合，会在Rel p50与p52同源二聚体存在时得到显著增强。与此结论一致，体外实验（in vitro）中Rel同源二聚体以依赖于TFII-I的方式增强HIV-1的转录活性。本研究结果表明，Rel二聚体可通过两种途径调控HIV-1的转录：其一，通过结合位于-104至-80区域的κB增强子位点，NF-κB p50:p65可参与经典的转录激活通路；其二，诸如p50或p52这类Rel二聚体，可结合至起始子序列，以调控特定预起始复合物（preinitiation complexes）组分的从头结合过程。上述研究结果，以及其他基因起始子区域存在Rel结合位点这一现象，均提示Rel蛋白在决定转录调控的早期事件中发挥关键作用。图像：