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首页> 外文期刊>Molecular and Cellular Biology >Direct Association and Nuclear Import of the Hepatitis B Virus X Protein with the NF-κB Inhibitor IκBα
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Direct Association and Nuclear Import of the Hepatitis B Virus X Protein with the NF-κB Inhibitor IκBα

机译：乙型肝炎病毒X蛋白与NF-κB抑制剂IκBα的直接缔合和核导入

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The X protein of hepatitis B virus (HBV) is a transcriptional activator which is required for infection and may play an important role in HBV-associated hepatocarcinogenesis. It has been suggested that X acts as a nuclear coactivator or stimulates several signal transduction pathways by acting in the cytoplasm. One of these pathways leads to the nuclear translocation of NF-κB. A recent report indicates that X activates NF-κB by acting on two cytoplasmic inhibitors of this family of transcription factors: IκBα and the precursor/inhibitor p105. We demonstrate here that X directly interacts with IκBα, which is able to transport it to the nucleus by a piggyback mechanism. This transport requires a region of IκBα (the second ankyrin repeat) which has been demonstrated to be involved in its nuclear import following NF-κB activation. Using deletion mutants, we showed that amino acids 249 to 253 of IκBα (located in the C-terminal part of the sixth ankyrin repeat) play a critical role in the interaction with X. This small region overlaps one of the domains of IκBα mediating the interaction with the p50 and p65 subunits of NF-κB and is also close to the nuclear export sequence of IκBα, therefore providing a potential explanation for the nuclear accumulation of IκBα with X. This association can also be observed upon the induction of endogenous IκBα by tumor necrosis factor alpha (TNF-α) treatment of Chang cells expressing X. In accordance with this observation, band shift analysis indicates that X induces a sustained NF-κB activation following TNF-α treatment, probably by preventing the reassociation of newly synthesized nuclear IκBα with DNA-bound NF-κB complexes.
机译：乙型肝炎病毒（HBV）的X蛋白是一种转录激活因子，是感染所必需的，并且可能在HBV相关的肝癌发生中起重要作用。已经建议X通过在细胞质中起作用而充当核共激活剂或刺激几种信号转导途径。这些途径之一导致NF-κB的核易位。最近的报道表明，X通过作用于该转录因子家族的两种胞质抑制剂：IκBα和前体/抑制剂p105来激活NF-κB。我们在这里证明X直接与IκBα相互作用，后者能够通过背负机制将其转运至核。这种转运需要一个IκBα（第二个锚蛋白重复序列​​）区域，该区域已被证明与NF-κB激活后的核输入有关。使用缺失突变体，我们发现IκBα的249至253位氨基酸（位于第六个锚蛋白重复序列​​的C端部分）在与X的相互作用中起关键作用。这个小区域与IκBα的一个域重叠，介导了IκBα的结构域。与NF-κB的p50和p65亚基相互作用，并且也接近IκBα的核输出序列，因此为X引起IκBα的核积累提供了可能的解释。这种关联也可以通过内源性IκBα的诱导而观察到。肿瘤坏死因子α（TNF-α）处理表达X的Chang细胞。根据此观察，带移分析表明X可以在TNF-α处理后诱导持续的NF-κB活化，这可能是通过阻止新合成的核的重新结合来实现的。 IκBα与DNA结合的NF-κB复合物。

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