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首页> 外文期刊>Journal of Molecular Biology >HTLV-1 HBZ protein deregulates interactions between cellular factors and the KIX domain of p300/CBP.
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HTLV-1 HBZ protein deregulates interactions between cellular factors and the KIX domain of p300/CBP.

机译：HTLV-1 HBZ蛋白调节细胞因子与p300 / CBP的KIX域之间的相互作用。

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The complex retrovirus human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia. Deregulation of cellular transcription is thought to be an important step for T-cell transformation caused by viral infection. HTLV-1 basic leucine zipper factor (HBZ) is one of the viral proteins believed to be involved in this process, as it deregulates the expression of numerous cellular genes. In the context of the provirus, HBZ represses HTLV-1 transcription, in part, by binding to the homologous cellular coactivators p300 and CBP. These coactivators play a central role in transcriptional regulation. In this study, we determined that HBZ binds with high affinity to the KIX domain of p300/CBP. This domain contains two binding surfaces that are differentially targeted by multiple cellular factors. We show that two phiXXphiphi motifs in the activation domain of HBZ mediate binding to a single surface of the KIX domain, the mixed-lineage leukemia (MLL) binding surface. Formation of this interaction inhibits binding of MLL to the KIX domain while enhancing the binding of the transcription factor c-Myb to the opposite surface of KIX. Consequently, HBZ inhibits transcriptional activation mediated by MLL and enhances activation mediated by c-Myb. CREB, which binds the same surface of KIX as c-Myb, also exhibited an increase in activity through HBZ. These results indicate that HBZ is able to alter gene expression by competing with transcription factors for the occupancy of one surface of KIX while enhancing the binding of factors to the other surface.
机译：复杂的逆转录病毒人1型T细胞白血病病毒（HTLV-1）是成人T细胞白血病的病原体。细胞转录失调被认为是由病毒感染引起的T细胞转化的重要步骤。 HTLV-1碱性亮氨酸拉链因子（HBZ）是一种病毒蛋白，被认为与该过程有关，因为它可以调节许多细胞基因的表达。在原病毒的情况下，HBZ部分通过与同源细胞共激活因子p300和CBP结合来抑制HTLV-1转录。这些共激活因子在转录调控中起着核心作用。在这项研究中，我们确定HBZ与p300 / CBP的KIX域具有高亲和力。该结构域包含两个被多个细胞因子差异靶向的结合表面。我们显示在HBZ的激活域中的两个phiXXphiphi主题介导结合到KIX域的单个表面，即混合谱系白血病（MLL）结合表面。这种相互作用的形成抑制了MLL与KIX结构域的结合，同时增强了转录因子c-Myb与KIX的相反表面的结合。因此，HBZ抑制了MLL介导的转录激活，并增强了c-Myb介导的激活。与c-Myb结合在KIX相同表面上的CREB，也通过HBZ表现出活性增加。这些结果表明，HBZ能够通过与转录因子竞争KIX的一个表面而改变基因表达，同时增强因子与另一表面的结合。

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