Crosstalk between hepatitis B virus X and high-mobility group box 1 facilitates autophagy in hepatocytes.
Crosstalk between hepatitis B virus X and high-mobility group box 1 facilitates autophagy in hepatocytes.
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乙型肝炎病毒X和高迁移率族盒1之间的串扰促进肝细胞自噬
DOI：
10.1002/1878-0261.12165
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发表时间：
2018-03
影响因子：
6.6
通讯作者：
Fan XG
中科院分区：
文献类型：
--
作者：
Fu S;Wang J;Hu X;Zhou RR;Fu Y;Tang D;Kang R;Huang Y;Sun L;Li N;Fan XG
B型肝炎病毒（HBV）X（HBx）蛋白是HBV触发的自噬的关键调节因子。然而，HBx诱导的表观遗传变化在自噬中的作用在很大程度上仍然未知。细胞质（Cyt）高迁移率族蛋白1（HMGB1）已被确定为自噬的正调控因子，其Cyt易位与其乙酰化状态密切相关。在这里，我们评估了HMGB1在HBx介导的自噬中的功能及其与组蛋白去乙酰化酶（HDAC）的相关性。使用具有HBx强制表达的细胞系，我们证明HBx上调HMGB1的表达，并通过乙酰化促进其Cyt易位以促进自噬。我们进一步确定了核HDAC活性和表达水平降低导致HBx促进的高乙酰化和随后的HMGB1易位的潜在机制。我们还确定了HDAC1亚型作为调节这种现象的关键因素。此外，HBx与细胞质中的HMGB1结合，从而引发肝细胞中的自噬。丙酮酸乙酯对HMGB1 Cyt易位的药理学抑制阻止了HBx诱导的自噬。这些结果证明了乙酰化HMGB1在肝细胞中HBx介导的自噬中的新功能。
Hepatitis B virus (HBV) X (HBx) protein is a pivotal regulator of HBV‐triggered autophagy. However, the role of HBx‐induced epigenetic changes in autophagy remains largely unknown. The cytoplasmic (Cyt) high‐mobility group box 1 (HMGB1) has been identified as a positive regulator of autophagy, and its Cyt translocation is closely associated with its acetylation status. Here, we evaluated the function of HMGB1 in HBx‐mediated autophagy and its association with histone deacetylase (HDAC). Using cell lines with enforced expression of HBx, we demonstrated that HBx upregulated the expression of HMGB1 and promoted its Cyt translocation by acetylation to facilitate autophagy. We further identified the underlying mechanism by which decreased nuclear HDAC activity and expression levels contribute to the HBx‐promoted hyperacetylation and subsequent translocation of HMGB1. We also identified the HDAC1 isoform as a critical factor in regulating this phenomenon. In addition, HBx bound to HMGB1 in the cytoplasm, which triggered autophagy in hepatocytes. Pharmacological inhibition of HMGB1 Cyt translocation with ethyl pyruvate prevented HBx‐induced autophagy. These results demonstrate a novel function of acetylated HMGB1 in HBx‐mediated autophagy in hepatocytes.
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影响因子：
5.4
作者：
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Jestin, Jean-Luc
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8
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作者：
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通讯作者：
Palmer, Dupeh R.