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      Protein Arginine Methyltransferases (PRMTs): Promising Targets for the Treatment of Pulmonary Disorders

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          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.

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          Most cited references117

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          Live or let die: the cell's response to p53.

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            Control of apoptosis by p53.

            The p53 tumor suppressor acts to integrate multiple stress signals into a series of diverse antiproliferative responses. One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance. p53 apparently promotes apoptosis through transcription-dependent and -independent mechanisms that act in concert to ensure that the cell death program proceeds efficiently. Moreover, the apoptotic activity of p53 is tightly controlled, and is influenced by a series of quantitative and qualitative events that influence the outcome of p53 activation. Interestingly, other p53 family members can also promote apoptosis, either in parallel or in concert with p53. Although incomplete, our current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type. Understanding this network in more detail will provide insights into cancer and other diseases, and will identify strategies to improve their therapeutic treatment.
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              Regulation of transcription by a protein methyltransferase.

              The p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors. Coactivator-associated arginine methyltransferase 1 (CARM1), a previously unidentified protein that binds to the carboxyl-terminal region of p160 coactivators, enhanced transcriptional activation by nuclear receptors, but only when GRIP1 or SRC-1a was coexpressed. Thus, CARM1 functions as a secondary coactivator through its association with p160 coactivators. CARM1 can methylate histone H3 in vitro, and a mutation in the putative S-adenosylmethionine binding domain of CARM1 substantially reduced both methyltransferase and coactivator activities. Thus, coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                2012
                27 September 2012
                : 13
                : 10
                : 12383-12400
                Affiliations
                [1 ]Department of Biochemistry, Faculty of Medicine, University of Giessen Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany
                [2 ]Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus Liebig-University Giessen, Rudolf-Buchheim-Str. 7, D-35385 Giessen, Germany; E-Mail: anna.zakrzewicz@ 123456chiru.med.uni-giessen.de
                [3 ]Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Giessen, Germany; E-Mails: klaus.t.preissner@ 123456biochemie.med.uni-giessen.de (K.T.P.); malgorzata.wygrecka@ 123456innere.med.uni-giessen.de (M.W.)
                [4 ]Department of Internal Medicine, Faculty of Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Giessen, Germany; E-Mail: philipp.markart@ 123456innere.med.uni-giessen.de
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: dariusz.zakrzewicz@ 123456innere.med.uni-giessen.de ; Tel.: +49-641-99-47508; Fax: +49-641-99-47509.
                Article
                ijms-13-12383
                10.3390/ijms131012383
                3497278
                23202904
                ea119228-3881-4e15-998f-4cf2ccfd3685
                © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0).

                History
                : 03 September 2012
                : 19 September 2012
                : 19 September 2012
                Categories
                Review

                Molecular biology
                prmt,chronic lung disease,protein arginine methylation
                Molecular biology
                prmt, chronic lung disease, protein arginine methylation

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