Arginine Methylation: the Promise of a 'silver Bullet' for Brain Tumours?

Overview

Journal Amino Acids

Specialty Biochemistry

Date 2021 Jan 6

PMID 33404912

Citations 11

Authors

Sabrina F Samuel

Antonia Barry

John Greenman

Pedro Beltran-Alvarez

Affiliations

Soon will be listed here.

Abstract

Despite intense research efforts, our pharmaceutical repertoire against high-grade brain tumours has not been able to increase patient survival for a decade and life expectancy remains at less than 16 months after diagnosis, on average. Inhibitors of protein arginine methyltransferases (PRMTs) have been developed and investigated over the past 15 years and have now entered oncology clinical trials, including for brain tumours. This review collates recent advances in the understanding of the role of PRMTs and arginine methylation in brain tumours. We provide an up-to-date literature review on the mechanisms for PRMT regulation. These include endogenous modulators such as alternative splicing, miRNA, post-translational modifications and PRMT-protein interactions, and synthetic inhibitors. We discuss the relevance of PRMTs in brain tumours with a particular focus on PRMT1, -2, -5 and -8. Finally, we include a future perspective where we discuss possible routes for further research on arginine methylation and on the use of PRMT inhibitors in the context of brain tumours.

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References

Xu J, Wang A, Oses-Prieto J, Makhijani K, Katsuno Y, Pei M . Arginine Methylation Initiates BMP-Induced Smad Signaling. Mol Cell. 2013; 51(1):5-19. PMC: 3951972. DOI: 10.1016/j.molcel.2013.05.004. View

Bhuripanyo K, Wang Y, Liu X, Zhou L, Liu R, Duong D . Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer. Sci Adv. 2018; 4(1):e1701393. PMC: 5756662. DOI: 10.1126/sciadv.1701393. View

Chen M, Qu X, Zhang Z, Wu H, Qin X, Li F . Cross-talk between Arg methylation and Ser phosphorylation modulates apoptosis signal-regulating kinase 1 activation in endothelial cells. Mol Biol Cell. 2016; 27(8):1358-66. PMC: 4831888. DOI: 10.1091/mbc.E15-10-0738. View

Morales Y, Caceres T, May K, Hevel J . Biochemistry and regulation of the protein arginine methyltransferases (PRMTs). Arch Biochem Biophys. 2015; 590:138-152. DOI: 10.1016/j.abb.2015.11.030. View

Kumar A, Zhong Y, Albrecht A, Sang P, Maples A, Liu Z . Actin R256 Mono-methylation Is a Conserved Post-translational Modification Involved in Transcription. Cell Rep. 2020; 32(13):108172. PMC: 8860185. DOI: 10.1016/j.celrep.2020.108172. View

Kaley T, Panageas K, Mellinghoff I, Nolan C, Gavrilovic I, DeAngelis L . Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. J Neurooncol. 2019; 144(2):403-407. PMC: 7493746. DOI: 10.1007/s11060-019-03243-7. View

Fong J, Pignata L, Goy P, Kawabata K, Chun-Wei Lee S, Koh C . Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation. Cancer Cell. 2019; 36(2):194-209.e9. PMC: 7194031. DOI: 10.1016/j.ccell.2019.07.003. View

Chittka A . Dynamic distribution of histone H4 arginine 3 methylation marks in the developing murine cortex. PLoS One. 2010; 5(11):e13807. PMC: 2972221. DOI: 10.1371/journal.pone.0013807. View

Rajaratnam V, Islam M, Yang M, Slaby R, Ramirez H, Mirza S . Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments. Cancers (Basel). 2020; 12(4). PMC: 7226351. DOI: 10.3390/cancers12040937. View

10.

Banasavadi-Siddegowda Y, Russell L, Frair E, Karkhanis V, Relation T, Yoo J . PRMT5-PTEN molecular pathway regulates senescence and self-renewal of primary glioblastoma neurosphere cells. Oncogene. 2016; 36(2):263-274. PMC: 5240810. DOI: 10.1038/onc.2016.199. View

11.

Hevel J, Price O . Rapid and direct measurement of methyltransferase activity in about 30 min. Methods. 2019; 175:3-9. DOI: 10.1016/j.ymeth.2019.10.002. View

12.

Simandi Z, Czipa E, Horvath A, Koszeghy A, Bordas C, Poliska S . PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology. Stem Cells. 2014; 33(3):726-41. DOI: 10.1002/stem.1894. View

13.

Pak M, Lakowski T, Thomas D, Vhuiyan M, Husecken K, Frankel A . A protein arginine N-methyltransferase 1 (PRMT1) and 2 heteromeric interaction increases PRMT1 enzymatic activity. Biochemistry. 2011; 50(38):8226-40. DOI: 10.1021/bi200644c. View

14.

Su X, Zhu G, Ding X, Lee S, Dou Y, Zhu B . Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1. Genes Dev. 2014; 28(6):622-36. PMC: 3967050. DOI: 10.1101/gad.233239.113. View

15.

Radzisheuskaya A, Shliaha P, Grinev V, Lorenzini E, Kovalchuk S, Shlyueva D . PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia. Nat Struct Mol Biol. 2019; 26(11):999-1012. PMC: 6858565. DOI: 10.1038/s41594-019-0313-z. View

16.

Robin-Lespinasse Y, Sentis S, Kolytcheff C, Rostan M, Corbo L, Le Romancer M . hCAF1, a new regulator of PRMT1-dependent arginine methylation. J Cell Sci. 2007; 120(Pt 4):638-47. DOI: 10.1242/jcs.03357. View

17.

Han X, Li R, Zhang W, Yang X, Wheeler C, Friedman G . Expression of PRMT5 correlates with malignant grade in gliomas and plays a pivotal role in tumor growth in vitro. J Neurooncol. 2014; 118(1):61-72. PMC: 4076054. DOI: 10.1007/s11060-014-1419-0. View

18.

Chang B, Chen Y, Zhao Y, Bruick R . JMJD6 is a histone arginine demethylase. Science. 2007; 318(5849):444-7. DOI: 10.1126/science.1145801. View

19.

Jeong H, Lee S, Lee H, Kim H, Vuong T, Cho H . Prmt7 promotes myoblast differentiation via methylation of p38MAPK on arginine residue 70. Cell Death Differ. 2019; 27(2):573-586. PMC: 7206020. DOI: 10.1038/s41418-019-0373-y. View

20.

Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee K . Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics. 2013; 13(1):372-87. PMC: 3879628. DOI: 10.1074/mcp.O113.027870. View