Protein Arginine Methyltransferases (PRMTs): promising targets for the treatment of pulmonary disorders

Abstract

Protein arginine methylation is a novel posttranslational modification that plays a pivotal role in a variety of intracellular events, such as signal transduction, protein-protein interaction and transcriptional regulation, either by the direct regulation of protein function or by metabolic products originating from protein arginine methylation that influence nitric oxide (NO)-dependent processes. A growing body of evidence suggests that both mechanisms are implicated in cardiovascular and pulmonary diseases. This review will present and discuss recent research on PRMTs and the methylation of non-histone proteins and its consequences for the pathogenesis of various lung disorders, including lung cancer, pulmonary fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease and asthma. This article will also highlight novel directions for possible future investigations to evaluate the functional contribution of arginine methylation in lung homeostasis and disease.

Figure 1

The mechanism of protein arginine methylation in mammalian cells. L-Arg can be monomethylated on a guanidino nitrogen atom by all protein arginine methyltransferases (PRMTs). Type I PRMTs catalyze the formation of asymmetric dimethylarginine, while type II PRMTs generate symmetric dimmethylarginine. The donor of methyl groups is S-adenosylmethionine (AdoMet), which is further converted to S-adenosylhomocysteine (AdoHcy).

Figure 2

Dysregulation of PRMTs in human and experimental pulmonary diseases. Members of the PRMT family and potential mechanisms of their action in the development and progression of pulmonary diseases (PD) are indicated. Arrows demonstrate PRMTs expression status, which has previously been reported in the literature. ↑, enhanced expression; ↓, impaired expression.