Phosphatase of regenerating liver maintains cellular magnesium homeostasis

Abstract

Phosphatase of regenerating liver (PRL) is highly expressed in malignant cancers and promotes cancer progression. Recent studies have suggested its functional relationship with Mg2+, but the importance and molecular details of this relationship remain unknown. Here, we report that PRL expression is regulated by Mg2+ and PRL protects cells from apoptosis under Mg2+-depleted conditions. When cultured cells were subjected to Mg2+ 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 Mg2+ depletion. Imaging analyses with a fluorescent probe for Mg2+ showed that PRL knockdown severely reduced intracellular Mg2+ levels, indicating a role for PRL in maintaining intracellular Mg2+. We also examined the mechanism of augmented expression of PRL proteins and found that PRL mRNA transcription was stimulated by Mg2+ 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 Mg2+ homeostasis.