Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
Biochem J. 2018 Mar 26;475(6):1129-1139. doi: 10.1042/BCJ20170756.
Phosphatase of regenerating liver (PRL) is highly expressed in malignant cancers and promotes cancer progression. Recent studies have suggested its functional relationship with Mg, but the importance and molecular details of this relationship remain unknown. Here, we report that PRL expression is regulated by Mg and PRL protects cells from apoptosis under Mg-depleted conditions. When cultured cells were subjected to Mg depletion, endogenous PRL protein levels increased significantly. siRNA-mediated knockdown of endogenous PRL did not significantly affect cell proliferation under normal culture conditions, but it increased cell death after Mg depletion. Imaging analyses with a fluorescent probe for Mg showed that PRL knockdown severely reduced intracellular Mg levels, indicating a role for PRL in maintaining intracellular Mg We also examined the mechanism of augmented expression of PRL proteins and found that mRNA transcription was stimulated by Mg depletion. A series of analyses revealed the activation and the crucial importance of signal transducer and activator of transcription 1 in this process. Collectively, these results implicate PRL in maintaining cellular Mg homeostasis.
肝再生磷酸酶（PRL）在恶性肿瘤中高度表达，促进癌症进展。最近的研究表明它与 Mg 具有功能关系，但这种关系的重要性和分子细节尚不清楚。在这里，我们报告 PRL 的表达受 Mg 调节，并且 PRL 在 Mg 耗竭条件下保护细胞免于凋亡。当培养的细胞受到 Mg 耗竭时，内源性 PRL 蛋白水平显著增加。siRNA 介导的内源性 PRL 敲低在正常培养条件下对细胞增殖没有显著影响，但在 Mg 耗竭后增加了细胞死亡。用 Mg 的荧光探针进行成像分析表明，PRL 敲低严重降低了细胞内的 Mg 水平，表明 PRL 在维持细胞内 Mg 中起作用。我们还研究了 PRL 蛋白表达增强的机制，发现 Mg 耗竭刺激 mRNA 转录。一系列分析揭示了信号转导和转录激活因子 1 在这一过程中的激活和关键重要性。总之，这些结果表明 PRL 参与维持细胞内 Mg 稳态。
