The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation
The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation
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DOI：
10.1016/j.bbrc.2009.10.129
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发表时间：
2009-12-25
影响因子：
3.1
通讯作者：
Fantappie, Marcelo Rosado
中科院分区：
文献类型：
--
作者：
Carneiro, Vitor Coutinho;Maciel, Renata de Moraes;Fantappie, Marcelo Rosado
曼氏血吸虫HMGB 1（SmHMGB 1）被发现是寄生虫组蛋白乙酰转移酶SmGCN 5和SmCBP 1的底物。我们发现，全长SmHMGB 1，以及它的HMG盒B（但不是HMG盒A）在体外乙酰化SmGCN 5和SmCBP 1。然而，SmCBP 1能够乙酰化这两种底物比SmGCN 5更有效。有趣的是，SmHMGB 1的C-末端酸性尾（SmHMGB 1 Delta C）的去除导致蛋白质的乙酰化增加。我们通过哺乳动物细胞转染实验表明，丁酸钠（NaB）处理后，SmHMGB 1和SmHMGB 1 Delta C从细胞核转运到细胞质。重要的是，NaB处理后，SmHMGB 1也存在于细胞外。总之，我们的数据表明，SmHMGB 1的乙酰化在细胞运输中发挥作用，最终分泌到细胞外环境。对SmHMGB 1乙酰化在血吸虫病发病机制中的可能作用进行了讨论。(C)2009爱思唯尔公司All rights reserved.
Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1 Delta C) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1 Delta C were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1 was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed. (C) 2009 Elsevier Inc. All rights reserved.