Universität zu Köln

Zakrzewicz, Dariusz, Didiasova, Miroslava, Krueger, Marcus ORCID: 0000-0003-2008-4582, Giaimo, Benedetto Daniele, Borggrefe, Tilman, Mieth, Maren, Hocke, Andreas C., Zakrzewicz, Anna, Schaefer, Liliana ORCID: 0000-0002-3318-3005, Preissner, Klaus T. and Wygrecka, Malgorzata ORCID: 0000-0002-3656-2932 (2018). Protein arginine methyltransferase 5 mediates enolase-1 cell surface trafficking in human lung adenocarcinoma cells. Biochim. Biophys. Acta-Mol. Basis Dis., 1864 (5). S. 1816 - 1828. AMSTERDAM: ELSEVIER. ISSN 1879-260X

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Abstract

Objectives: Enolase-l-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 (R5Ome) within Eno-1. The Eno-1R5Ome 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, Eno1R5Ome was essential for cancer cell motility since the replacement of Eno-1 R50 by lysine or the suppression of PRMT 5 activity diminished Eno-l-triggered cell invasion. Conclusions: LPS-triggered Eno-1R5Ome enhances Eno-1 cell surface levels and thus potentiates the invasive properties of cancer cells. Strategies to target Eno-1R5Ome may offer novel therapeutic approaches to attenuate tumor metastasis in cancer patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zakrzewicz, Dariusz UNSPECIFIED UNSPECIFIED UNSPECIFIED Didiasova, Miroslava UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Giaimo, Benedetto Daniele UNSPECIFIED UNSPECIFIED UNSPECIFIED Borggrefe, Tilman UNSPECIFIED UNSPECIFIED UNSPECIFIED Mieth, Maren UNSPECIFIED UNSPECIFIED UNSPECIFIED Hocke, Andreas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zakrzewicz, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Liliana UNSPECIFIED orcid.org/0000-0002-3318-3005 UNSPECIFIED Preissner, Klaus T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wygrecka, Malgorzata UNSPECIFIED orcid.org/0000-0002-3656-2932 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-186783
DOI:	10.1016/j.bbadis.2018.02.021
Journal or Publication Title:	Biochim. Biophys. Acta-Mol. Basis Dis.
Volume:	1864
Number:	5
Page Range:	S. 1816 - 1828
Date:	2018
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1879-260X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PLASMINOGEN RECEPTORS; LYSINE-ACETYLATION; ALPHA-ENOLASE; METHYLATION; PRMT5; EXPRESSION; INHIBITOR; ROLES; INFLAMMATION; ADHESION Multiple languages Biochemistry & Molecular Biology; Biophysics; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18678