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J Biol Chem. 2015 Jun 12;290(24):14915-26. doi: 10.1074/jbc.M115.651380. Epub 2015 Apr 24.

Redox Control of Protein Arginine Methyltransferase 1 (PRMT1) Activity.

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From the Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322.
the Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260, and the New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, New York 14203.
From the Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322,


Elevated levels of asymmetric dimethylarginine (ADMA) correlate with risk factors for cardiovascular disease. ADMA is generated by the catabolism of proteins methylated on arginine residues by protein arginine methyltransferases (PRMTs) and is degraded by dimethylarginine dimethylaminohydrolase. Reports have shown that dimethylarginine dimethylaminohydrolase activity is down-regulated and PRMT1 protein expression is up-regulated under oxidative stress conditions, leading many to conclude that ADMA accumulation occurs via increased synthesis by PRMTs and decreased degradation. However, we now report that the methyltransferase activity of PRMT1, the major PRMT isoform in humans, is impaired under oxidative conditions. Oxidized PRMT1 displays decreased activity, which can be rescued by reduction. This oxidation event involves one or more cysteine residues that become oxidized to sulfenic acid (-SOH). We demonstrate a hydrogen peroxide concentration-dependent inhibition of PRMT1 activity that is readily reversed under physiological H2O2 concentrations. Our results challenge the unilateral view that increased PRMT1 expression necessarily results in increased ADMA synthesis and demonstrate that enzymatic activity can be regulated in a redox-sensitive manner.


ADMA; PRMT1; arginine methylation; endothelial dysfunction; hydrogen peroxide; oxidative stress; posttranslational modification (PTM); protein arginine methyltransferase; redox regulation; sulfenic acid

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