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Inhibiting arginine methylation as a tool to investigate cross-talk with methylation and acetylation post-translational modifications in a glioblastoma cell line

Marsden, Alistair; Samuel, Sabrina Francesca; Marsden, Alistair James; Deepak, Srihari; Rivero, Francisco; Greenman, John; Beltran-Alvarez, Pedro

Authors

Alistair Marsden

Sabrina Francesca Samuel s.samuel@2017.hull.ac.uk (S.F.S.)

Alistair James Marsden a.marsden@2014.hull.ac.uk (A.J.M.)

Srihari Deepak Srihari.Deepak@hey.nhs.uk

Francisco Rivero francisco.rivero@hyms.ac.uk * Correspondence: p.beltran-alvarez@hull.ac.uk



Abstract

Glioblastomas (GBM) are the most common grade 4 brain tumours; patients have very poor prognosis with an average survival of 15 months after diagnosis. Novel research lines have begun to explore aberrant protein arginine methylation (ArgMe) as a possible therapeutic target in GBM and ArgMe inhibitors are currently in clinical trials. Enzymes known as protein arginine methyltransferases (PRMT1-9) can lead to mono-or di-ArgMe, and in the latter case symmetric or asymmetric dimethylation (SDMA and ADMA, respectively). Using the most common GBM cell line, we have profiled the expression of PRMTs, used ArgMe inhibitors as tools to investigate post-translational modifications cross-talk and measured the effect of ArgMe inhibitors on cell viability. We have identified novel SDMA events upon inhibition of ADMA in GBM cells and spheroids. We have observed cross-talk between ADMA and lysine acetylation in GBM cells and platelets. Treatment of GBM cells with furamidine, a PRMT1 inhibitor, reduces cell viability in 2D and 3D models. These data provide new molecular understanding of a disease with unmet clinical needs.

Journal Article Type Article
Publication Date Dec 1, 2018
Print ISSN 2227-7382
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 6
Issue 4
Article Number 44
Institution Citation Samuel, S. F., Marsden, A. J., Deepak, S., Rivero, F., Greenman, J., & Beltran-Alvarez, P. (2018). Inhibiting arginine methylation as a tool to investigate cross-talk with methylation and acetylation post-translational modifications in a glioblastoma cell line. Proteomes, 6(4), https://doi.org/10.3390/proteomes6040044
DOI https://doi.org/10.3390/proteomes6040044
Keywords Arginine methylation; Cross-talk; Glioblastoma; Inhibitor; Lysine acetylation
Publisher URL https://www.mdpi.com/2227-7382/6/4/44

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Copyright Statement
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).







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