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

Simona Nanni, Annarita Favia, Luisa Salvatori, Lisa K. Iwamoto-Stohl, Sergio Valente, Antonello Mai, Fiorella Scagnoli, Rosaria Anna Fontanella, Pierangela Totta, Sergio Nasi, Barbara Illi

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8 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)15925-N/A
RivistaScientific Reports
Volume9
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Protein Arginine Methyltransferases

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