ArticleThe Journal of biological chemistry2016
Inhibition of PRL-2·CNNM3 Protein Complex Formation Decreases Breast Cancer Proliferation and Tumor Growth.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Article
- Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.Biochemical Society transactions · 2026Review
- Leishmania donovani's protein tyrosine phosphatases interact with DUF21 and respond to environmental magnesium.The FEBS journal · 2026Article
- Article
- TUSC3 regulates ERMA-mediated MgNature communications · 2025Article
- microRNAs Regulate Cellular Magnesium by Tuning Expression of the Plasma Membrane Protein CNNM4.ACS chemical biology · 2025Article
- The PACT Network: PRL, ARL, CNNM, and TRPM Proteins in Magnesium Transport and Disease.International journal of molecular sciences · 2025Review
- Differential regulation of magnesium transporters Slc41, Cnnm and Trpm6-7 in the kidney of salmonids may represent evolutionary adaptations to high salinity environments.BMC genomics · 2024Article
- Development of a high-throughput screening system targeting the protein-protein interactions between PRL and CNNM.Scientific reports · 2024Article
- PTP4A2 Promotes Glioblastoma Progression and Macrophage Polarization under Microenvironmental Pressure.Cancer research communications · 2024Article
- Micronutrient Status and Breast Cancer: A Narrative Review.International journal of molecular sciences · 2024Review
- Phosphatase and Pseudo-Phosphatase Functions of Phosphatase of Regenerating Liver 3 (PRL-3) Are Insensitive to Divalent Metals In Vitro.ACS omega · 2023Article
- PRL-1/2 phosphatases control TRPM7 magnesium-dependent function to regulate cellular bioenergetics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Phosphatase-independent role of phosphatase of regenerating liver in cancer progression.Cancer science · 2023Review
- CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells.PLoS biology · 2021Article
- The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics.eLife · 2021Article
- Article
- Structural basis for the MgScience advances · 2021Article
- Membrane Transporters and Channels in Melanoma.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Downregulated Expression of miRNA-130a-5p Aggravates Hepatoma Progression via Targeting PTP4A2.Computational and mathematical methods in medicine · 2021Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The oncogenic phosphatase of regenerating liver 2 (PRL-2) has been shown to regulate intracellular magnesium levels by forming a complex through an extended amino acid loop present in the Bateman module of the CNNM3 magnesium transporter. Here we identified highly conserved residues located on this amino acid loop critical for the binding with PRL-2. A single point mutation (D426A) of one of those critical amino acids was found to completely disrupt PRL-2·human Cyclin M 3 (CNNM3) complex formation. Whole-cell voltage clamping revealed that expression of CNNM3 influenced the surface current, whereas overexpression of the binding mutant had no effect, indicating that the binding of PRL-2 to CNNM3 is important for the activity of the complex. Interestingly, overexpression of the CNNM3 D426A-binding mutant in cancer cells decreased their ability to proliferate under magnesium-deprived situations and under anchorage-independent growth conditions, demonstrating a PRL-2·CNNM3 complex-dependent oncogenic advantage in a more stringent environment. We further confirmed the importance of this complex in vivo using an orthotopic xenograft breast cancer model. Finally, because molecular modeling showed that the Asp-426 side chain in CNNM3 buries into the catalytic cavity of PRL-2, we showed that a PRL inhibitor could abrogate complex formation, resulting in a decrease in proliferation of human breast cancer cells. In summary, we provide evidence that this fundamental regulatory aspect of PRL-2 in cancer cells could potentially lead to broadly applicable and innovative therapeutic avenues.
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