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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

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

Authors

Sabrina Francesca Samuel

Alistair James Marsden

Srihari Deepak

Profile image of Pedro Beltran-Alvarez

Dr Pedro Beltran-Alvarez P.Beltran-Alvarez@hull.ac.uk
Senior Lecturer in Health and Climate Change and Programme co-Director of the MSc Health and Climate Change



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.

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), Article 44. https://doi.org/10.3390/proteomes6040044

Journal Article Type Article
Acceptance Date Oct 17, 2018
Online Publication Date Oct 20, 2018
Publication Date Dec 1, 2018
Deposit Date Oct 22, 2018
Publicly Available Date Oct 22, 2018
Journal Proteomes
Electronic ISSN 2227-7382
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 6
Issue 4
Article Number 44
DOI https://doi.org/10.3390/proteomes6040044
Keywords Arginine methylation; Cross-talk; Glioblastoma; Inhibitor; Lysine acetylation
Public URL https://hull-repository.worktribe.com/output/1124772
Publisher URL https://www.mdpi.com/2227-7382/6/4/44
Contract Date Oct 22, 2018

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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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