HIV-1 Tat protein induces glial cell autophagy through enhancement of BAG3 protein levels
HIV-1 Tat protein induces glial cell autophagy through enhancement of BAG3 protein levels
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DOI：
10.4161/15384101.2014.952959
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发表时间：
2014-12-01
期刊：
影响因子：
4.3
通讯作者：
Rosati, Alessandra
中科院分区：
文献类型：
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作者：
Bruno, Anna Paola;De Simone, Francesca Isabella;Rosati, Alessandra
BAG3蛋白在一些肿瘤细胞和正常细胞中被认为是一种抗凋亡和促自噬因子。我们之前已经证明，在HIV-1感染的胶质细胞和T淋巴细胞中，BAG3的表达会升高。在HIV-1蛋白中，Tat高度参与调节宿主细胞对病毒感染的反应。因此，我们研究了Tat蛋白在调节BAG3蛋白水平和自噬过程本身中的可能作用。在本报告中，我们发现转染Tat可提高胶质母细胞瘤细胞中的BAG3水平。此外，BAG3沉默可显著降低Tat诱导的LC3-II水平，增加亚G0/G1凋亡细胞的外观，这与BAG3在调节自噬/凋亡平衡中的作用一致。这些结果首次证明Tat蛋白能够通过增加人神经胶质细胞中的BAG3水平来刺激自噬。
BAG3 protein has been described as an anti-apoptotic and pro-autophagic factor in several neoplastic and normal cells. We previously demonstrated that BAG3 expression is elevated upon HIV-1 infection of glial and T lymphocyte cells. Among HIV-1 proteins, Tat is highly involved in regulating host cell response to viral infection. Therefore, we investigated the possible role of Tat protein in modulating BAG3 protein levels and the autophagic process itself. In this report, we show that transfection with Tat raises BAG3 levels in glioblastoma cells. Moreover, BAG3 silencing results in highly reducing Tat- induced levels of LC3-II and increasing the appearance of sub G0/G1 apoptotic cells, in keeping with the reported role of BAG3 in modulating the autophagy/apoptosis balance. These results demonstrate for the first time that Tat protein is able to stimulate autophagy through increasing BAG3 levels in human glial cells.