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The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells

Protein Arginine (R) methylation is the most common post-translational methylation in mammalian cells. Protein Arginine Methyltransferases (PRMT) 1 and 5 dimethylate their substrates on R residues, asymmetrically and symmetrically, respectively. They are ubiquitously expressed and play fundamental r...

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Autores principales: Favia, Annarita, Salvatori, Luisa, Nanni, Simona, Iwamoto-Stohl, Lisa K., Valente, Sergio, Mai, Antonello, Scagnoli, Fiorella, Fontanella, Rosaria Anna, Totta, Pierangela, Nasi, Sergio, Illi, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828805/
https://www.ncbi.nlm.nih.gov/pubmed/31685892
http://dx.doi.org/10.1038/s41598-019-52291-6
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author Favia, Annarita
Salvatori, Luisa
Nanni, Simona
Iwamoto-Stohl, Lisa K.
Valente, Sergio
Mai, Antonello
Scagnoli, Fiorella
Fontanella, Rosaria Anna
Totta, Pierangela
Nasi, Sergio
Illi, Barbara
author_facet Favia, Annarita
Salvatori, Luisa
Nanni, Simona
Iwamoto-Stohl, Lisa K.
Valente, Sergio
Mai, Antonello
Scagnoli, Fiorella
Fontanella, Rosaria Anna
Totta, Pierangela
Nasi, Sergio
Illi, Barbara
author_sort Favia, Annarita
collection PubMed
description Protein Arginine (R) methylation is the most common post-translational methylation in mammalian cells. Protein Arginine Methyltransferases (PRMT) 1 and 5 dimethylate their substrates on R residues, asymmetrically and symmetrically, respectively. They are ubiquitously expressed and play fundamental roles in tumour malignancies, including glioblastoma multiforme (GBM) which presents largely deregulated Myc activity. Previously, we demonstrated that PRMT5 associates with Myc in GBM cells, modulating, at least in part, its transcriptional properties. Here we show that Myc/PRMT5 protein complex includes PRMT1, in both HEK293T and glioblastoma stem cells (GSCs). We demonstrate that Myc is both asymmetrically and symmetrically dimethylated by PRMT1 and PRMT5, respectively, and that these modifications differentially regulate its stability. Moreover, we show that the ratio between symmetrically and asymmetrically dimethylated Myc changes in GSCs grown in stem versus differentiating conditions. Finally, both PRMT1 and PRMT5 activity modulate Myc binding at its specific target promoters. To our knowledge, this is the first work reporting R asymmetrical and symmetrical dimethylation as novel Myc post-translational modifications, with different functional properties. This opens a completely unexplored field of investigation in Myc biology and suggests symmetrically dimethylated Myc species as novel diagnostic and prognostic markers and druggable therapeutic targets for GBM.
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spelling pubmed-68288052019-11-12 The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells Favia, Annarita Salvatori, Luisa Nanni, Simona Iwamoto-Stohl, Lisa K. Valente, Sergio Mai, Antonello Scagnoli, Fiorella Fontanella, Rosaria Anna Totta, Pierangela Nasi, Sergio Illi, Barbara Sci Rep Article Protein Arginine (R) methylation is the most common post-translational methylation in mammalian cells. Protein Arginine Methyltransferases (PRMT) 1 and 5 dimethylate their substrates on R residues, asymmetrically and symmetrically, respectively. They are ubiquitously expressed and play fundamental roles in tumour malignancies, including glioblastoma multiforme (GBM) which presents largely deregulated Myc activity. Previously, we demonstrated that PRMT5 associates with Myc in GBM cells, modulating, at least in part, its transcriptional properties. Here we show that Myc/PRMT5 protein complex includes PRMT1, in both HEK293T and glioblastoma stem cells (GSCs). We demonstrate that Myc is both asymmetrically and symmetrically dimethylated by PRMT1 and PRMT5, respectively, and that these modifications differentially regulate its stability. Moreover, we show that the ratio between symmetrically and asymmetrically dimethylated Myc changes in GSCs grown in stem versus differentiating conditions. Finally, both PRMT1 and PRMT5 activity modulate Myc binding at its specific target promoters. To our knowledge, this is the first work reporting R asymmetrical and symmetrical dimethylation as novel Myc post-translational modifications, with different functional properties. This opens a completely unexplored field of investigation in Myc biology and suggests symmetrically dimethylated Myc species as novel diagnostic and prognostic markers and druggable therapeutic targets for GBM. Nature Publishing Group UK 2019-11-04 /pmc/articles/PMC6828805/ /pubmed/31685892 http://dx.doi.org/10.1038/s41598-019-52291-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Favia, Annarita
Salvatori, Luisa
Nanni, Simona
Iwamoto-Stohl, Lisa K.
Valente, Sergio
Mai, Antonello
Scagnoli, Fiorella
Fontanella, Rosaria Anna
Totta, Pierangela
Nasi, Sergio
Illi, Barbara
The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells
title The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells
title_full The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells
title_fullStr The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells
title_full_unstemmed The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells
title_short The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells
title_sort protein arginine methyltransferases 1 and 5 affect myc properties in glioblastoma stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828805/
https://www.ncbi.nlm.nih.gov/pubmed/31685892
http://dx.doi.org/10.1038/s41598-019-52291-6
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