Inhibiting Arginine Methylation as a Tool to Investigate Cross-Talk with Methylation and Acetylation Post-Translational Modifications in a Glioblastoma Cell Line

被引:9
作者
Samuel, Sabrina Francesca [1 ]
Marsden, Alistair James [1 ]
Deepak, Srihari [2 ,3 ]
Rivero, Francisco [3 ]
Greenman, John [1 ]
Beltran-Alvarez, Pedro [1 ]
机构
[1] Univ Hull, Biomed Sci, Fac Hlth Sci, Kingston Upon Hull HU6 7RX, N Humberside, England
[2] Hull Royal Infirm, Dept Neurosurg, Kingston Upon Hull HU3 2JZ, N Humberside, England
[3] Univ Hull, Hull York Med Sch, Fac Hlth Sci, Kingston Upon Hull HU6 7RX, N Humberside, England
来源
PROTEOMES | 2018年 / 6卷 / 04期
关键词
arginine methylation; cross-talk; glioblastoma; inhibitor; lysine acetylation;
D O I
10.3390/proteomes6040044
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:10
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