摘要
它一致地被看了那 oncoprotein p28GANK，它是在人的 hepatocellular 癌(HCC ) 的 overexpressed，在 HCC 的 tumorigenesis 起一个关键作用。然而，内在的机制仍然保持不清楚。这里，我们证明 p28GANK 在 endoplasmic 蜂窝胃导致的 HCC 房间禁止 apoptosis (嗯) 应力。在期间嗯应力， p28GANK 提高展开的蛋白质反应，支持嗯从翻译压抑的恢复，并且从而便于房间的能力应付压力条件。而且， p28GANK upregulates 调整葡萄糖的蛋白质 78 (GRP78 ) ，一把钥匙嗯女伴蛋白质，它随后提高合拢能力的 ER 并且支持恢复从嗯应力。我们也证明 p28GANK 增加 p38 激活 mitogen 的蛋白质 kinase 和 Akt phosphorylation，并且禁止原子因素 kappa B (NF-B ) 激活在下面嗯强调 upregulation，它接着贡献 GRP78。一起拿，我们的结果显示 p28GANK 禁止嗯在 HCC 房间的导致压力的 apoptosis，至少部分地，由提高适应反应和 GRP78 表示。我们建议 p28GANK 在 ER 压力条件下面为 HCC 前进有潜在的含意。
It has been shown that oncoprotein p28GANK, which is consistently overexpressed in human hepatocellular carcinoma （HCC）, plays a critical role in tumorigenesis of HCC. However, the underlying mechanism remains unclear. Here, we demonstrated that p28GANK inhibits apoptosis in HCC cells induced by the endoplasmic reticulum （ER） stress. During ER stress, p28GANK enhances the unfolded protein response, promotes ER recovery from translational repression, and thereby facilitates cell＇s ability to cope with the stress conditions. Furthermore, p28GANK upregulates glucose-regulated protein 78 （GRP78）, a key ER chaperone protein, which subsequently enhances the ER folding capacity and promotes recovery from ER stress. We also demonstrated that p28GANK increases p38 mitogen-activated protein kinase and Akt phosphorylation, and inhibits nuclear factor kappa B （NF-κB） activation under ER stress, which in turn contributes to GRP78 upregulation. Taken together, our results indicate that p28GANK inhibits ER stress-induced apoptosis in HCC cells, at least in part, by enhancing the adaptive response and GRP78 expression. We propose that p28GANK has potential implications for HCC progression under the ER stress conditions.
