Back to article: PRMT5 function and targeting in cancer


TABLE 1. Summary of PRMT5 substrates and the biological effect of their methylation by PRMT5.

“TS*” and “ND” indicate “Tumor suppressive” and “not determined”, respectively.

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31. Zhao Q, Rank G, Tan YT, Li H, Moritz RL, Simpson RJ, Cerruti L, Curtis DJ, Patel DJ, Allis CD, Cunningham JM, Jane SM (2009). PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat Struct Mol Biol 16(3): 304-311. 10.1038/nsmb.1568

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40. Fu T, Lv X, Kong Q, Yuan C (2017). A novel SHARPIN-PRMT5-H3R2me1 axis is essential for lung cancer cell invasion. Oncotarget 8(33): 54809-54820. 10.18632/oncotarget.18957

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42. Li Y, Chitnis N, Nakagawa H, Kita Y, Natsugoe S, Yang Y, Li Z, Wasik M, Klein-Szanto AJ, Rustgi AK, Diehl JA (2015). PRMT5 is required for lymphomagenesis triggered by multiple oncogenic drivers. Cancer Discov 5(3): 288-303. 10.1158/2159-8290.CD-14-0625

43. Cho EC, Zheng S, Munro S, Liu G, Carr SM, Moehlenbrink J, Lu YC, Stimson L, Khan O, Konietzny R, McGouran J, Coutts AS, Kessler B, Kerr DJ, Thangue NB (2012). Arginine methylation controls growth regulation by E2F-1. EMBO J 31(7): 1785-1797. 10.1038/emboj.2012.17

45. Wei H, Wang B, Miyagi M, She Y, Gopalan B, Huang DB, Ghosh G, Stark GR, Lu T (2013). PRMT5 dimethylates R30 of the p65 subunit to activate NF-kappaB. Proc Natl Acad Sci U S A 110(33): 13516-13521. 10.1073/pnas.1311784110

48. Hu D, Gur M, Zhou Z, Gamper A, Hung MC, Fujita N, Lan L, Bahar I, Wan Y (2015). Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis. Nat Commun 6: 8419. 10.1038/ncomms9419.

49. Liu L, Zhao X, Zhao L, Li J, Yang H, Zhu Z, Liu J, Huang G (2016). Arginine Methylation of SREBP1a via PRMT5 Promotes De Novo Lipogenesis and Tumor Growth. Cancer Res 76(5): 1260-1272. 10.1158/0008-5472.CAN-15-1766

51. Mounir Z, Korn JM, Westerling T, Lin F, Kirby CA, Schirle M, McAllister G, Hoffman G, Ramadan N, Hartung A, Feng Y, Kipp DR, Quinn C, Fodor M, Baird J, Schoumacher M, Meyer R, Deeds J, Buchwalter G, Stams T, Keen N, Sellers WR, Brown M, Pagliarini RA (2016). ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor. Elife 5: e13964. 10.7554/eLife.13964

52. Lu X, Fernando TM, Lossos C, Yusufova N, Liu F, Fontan L, Durant M, Geng H, Melnick J, Luo Y, Vega F, Moy V, Inghirami G, Nimer S, Melnick AM, Lossos IS (2018). PRMT5 interacts with the BCL6 oncoprotein and is required for germinal center formation and lymphoma cell survival. Blood 132(19): 2026-2039. 10.1182/blood-2018-02-831438

53. Tamiya H, Kim H, Klymenko O, Kim H, Feng Y, Zhang T, Han JY, Murao A, Snipas SJ, Jilaveanu L, Brown K, Kluger H, Zhang H, Iwai K, Ronai ZA (2018). SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth. J Clin Invest 128(1): 517-530. 10.1172/JCI95410

57. Radzisheuskaya A, Shliaha PV, Grinev V, Lorenzini E, Kovalchuk S, Shlyueva D, Gorshkov V, Hendrickson RC, Jensen ON, Helin K (2019). PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia. Nat Struct Mol Biol 26(11): 999-1012. 10.1038/s41594-019-0313-z

59. Meister G, Eggert C, Buhler D, Brahms H, Kambach C, Fischer U (2001). Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln. Curr Biol 11(24): 1990-1994. 10.1016/s0960-9822(01)00592-9

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80. Hsu JM, Chen CT, Chou CK, Kuo HP, Li LY, Lin CY, Lee HJ, Wang YN, Liu M, Liao HW, Shi B, Lai CC, Bedford MT, Tsai CH, Hung MC (2011). Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat Cell Biol 13(2): 174-181. 10.1038/ncb2158

81. Andreu-Perez P, Esteve-Puig R, de Torre-Minguela C, Lopez-Fauqued M, Bech-Serra JJ, Tenbaum S, Garcia-Trevijano ER, Canals F, Merlino G, Avila MA, Recio JA (2011). Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci Signal 4(190): ra58. 10.1126/scisignal.2001936

82. Calabretta S, Vogel G, Yu Z, Choquet K, Darbelli L, Nicholson TB, Kleinman CL, Richard S (2018). Loss of PRMT5 Promotes PDGFRalpha Degradation during Oligodendrocyte Differentiation and Myelination. Dev Cell 46(4): 426-440 e425. 10.1016/j.devcel.2018.06.025

84. Gulla A, Hideshima T, Bianchi G, Fulciniti M, Kemal Samur M, Qi J, Tai YT, Harada T, Morelli E, Amodio N, Carrasco R, Tagliaferri P, Munshi NC, Tassone P, Anderson KC (2018). Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma. Leukemia 32(4): 996-1002. 10.1038/leu.2017.334

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89. Guo Z, Zheng L, Xu H, Dai H, Zhou M, Pascua MR, Chen QM, Shen B (2010). Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nat Chem Biol 6(10): 766-773. 10.1038/nchembio.422

90. He W, Ma X, Yang X, Zhao Y, Qiu J, Hang H (2011). A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage. Nucleic Acids Res 39(11): 4719-4727. 10.1093/nar/gkq1264

91. Clarke TL, Sanchez-Bailon MP, Chiang K, Reynolds JJ, Herrero-Ruiz J, Bandeiras TM, Matias PM, Maslen SL, Skehel JM, Stewart GS, Davies CC (2017). PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination. Mol Cell 65(5): 900-916 e907. 10.1016/j.molcel.2017.01.019

92. Rehman I, Basu SM, Das SK, Bhattacharjee S, Ghosh A, Pommier Y, Das BB (2018). PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes. Nucleic Acids Res 46(11): 5601-5617. 10.1093/nar/gky291

93. Kim H, Kim H, Feng Y, Li Y, Tamiya H, Tocci S, Ronai ZA (2020). PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity. Sci Translat Med 12(551):eaaz5683. 10.1126/scitranslmed.aaz5683

103. Nagai Y, Ji MQ, Zhu F, Xiao Y, Tanaka Y, Kambayashi T, Fujimoto S, Goldberg MM, Zhang H, Li B, Ohtani T, Greene MI (2019). PRMT5 Associates With the FOXP3 Homomer and When Disabled Enhances Targeted p185(erbB2/neu) Tumor Immunotherapy. Front Immunol 10:174. 10.3389/fimmu.2019.00174

122. Azzouz TN, Pillai RS, Dapp C, Chari A, Meister G, Kambach C, Fischer U, Schumperli D (2005). Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm proteins with PRMT5 and SMN complexes. J Biol Chem 280(41): 34435-34440. 10.1074/jbc.M505077200

123. Pesiridis GS, Diamond E, Van Duyne GD (2009). Role of pICLn in methylation of Sm proteins by PRMT5. J Biol Chem 284(32): 21347-21359. 10.1074/jbc.M109.015578

134. Chen H, Lorton B, Gupta V, Shechter D (2017). A TGFbeta-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression. Oncogene 36(3): 373-386. 10.1038/onc.2016.205

135. Rengasamy M, Zhang F, Vashisht A, Song WM, Aguilo F, Sun Y, Li S, Zhang W, Zhang B, Wohlschlegel JA, Walsh MJ (2017). The PRMT5/WDR77 complex regulates alternative splicing through ZNF326 in breast cancer. Nucleic Acids Res 45(19): 11106-11120. 10.1093/nar/gkx727

136. Powers MA, Fay MM, Factor RE, Welm AL, Ullman KS (2011). Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4. Cancer Res 71(16): 5579-5587. 10.1158/0008-5472.CAN-11-0458

137. Fay MM, Clegg JM, Uchida KA, Powers MA, Ullman KS (2014). Enhanced arginine methylation of programmed cell death 4 protein during nutrient deprivation promotes tumor cell viability. J Biol Chem 289(25): 17541-17552. 10.1074/jbc.M113.541300

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