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Protein arginine methyltransferase 5 mediates enolase-1 cell surface trafficking in human lung adenocarcinoma cells
- Source :
- Biochimica et biophysica acta. Molecular basis of disease. 1864(5 Pt)
- Publication Year :
- 2017
-
Abstract
- Objectives Enolase-1-dependent cell surface proteolysis plays an important role in cell invasion. Although enolase-1 (Eno-1), a glycolytic enzyme, has been found on the surface of various cells, the mechanism responsible for its exteriorization remains elusive. Here, we investigated the involvement of post-translational modifications (PTMs) of Eno-1 in its lipopolysaccharide (LPS)-triggered trafficking to the cell surface. Results We found that stimulation of human lung adenocarcinoma cells with LPS triggered the monomethylation of arginine 50 (R50me) within Eno-1. The Eno-1R50me was confirmed by its interaction with the tudor domain (TD) from TD-containing 3 (TDRD3) protein recognizing methylarginines. Substitution of R50 with lysine (R50K) reduced Eno-1 association with epithelial caveolar domains, thereby diminishing its exteriorization. Similar effects were observed when pharmacological inhibitors of arginine methyltransferases were applied. Protein arginine methyltransferase 5 (PRMT5) was identified to be responsible for Eno-1 methylation. Overexpression of PRMT5 and caveolin-1 enhanced levels of membrane-bound extracellular Eno-1 and, conversely, pharmacological inhibition of PRMT5 attenuated Eno-1 cell-surface localization. Importantly, Eno-1R50me was essential for cancer cell motility since the replacement of Eno-1 R50 by lysine or the suppression of PRMT 5 activity diminished Eno-1-triggered cell invasion. Conclusions LPS-triggered Eno-1R50me enhances Eno-1 cell surface levels and thus potentiates the invasive properties of cancer cells. Strategies to target Eno-1R50me may offer novel therapeutic approaches to attenuate tumor metastasis in cancer patients.
- Subjects :
- 0301 basic medicine
Lipopolysaccharides
Protein-Arginine N-Methyltransferases
Methyltransferase
Tudor domain
Lung Neoplasms
Arginine
Cell
Caveolin 1
Adenocarcinoma of Lung
Adenocarcinoma
03 medical and health sciences
0302 clinical medicine
Extracellular
medicine
Biomarkers, Tumor
Humans
Molecular Biology
Chemistry
Protein arginine methyltransferase 5
Tumor Suppressor Proteins
Methylation
Cell biology
Neoplasm Proteins
DNA-Binding Proteins
Protein Transport
030104 developmental biology
medicine.anatomical_structure
A549 Cells
030220 oncology & carcinogenesis
Phosphopyruvate Hydratase
Cancer cell
Molecular Medicine
Subjects
Details
- ISSN :
- 09254439
- Volume :
- 1864
- Issue :
- 5 Pt
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta. Molecular basis of disease
- Accession number :
- edsair.doi.dedup.....f6542b718c6fcbc47ca93ea82d829f92