153. Cho E-C et al (2012) Arginine methylation controls growth regulation by E2F-1. EMBO J
31:1785–1797
154. Wei T-YW et al (2012) Protein arginine methyltransferase 5 is a potential oncoprotein that
upregulates G1 cyclins/cyclin-dependent kinases and the phosphoinositide 3-kinase/AKT
signaling cascade. Cancer Sci 103:1640–1650
155. Győrffy B et al (2013) Online survival analysis software to assess the prognostic value of
biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One 8:e82241
156. Bao X et al (2013) Overexpression of PRMT5 promotes tumor cell growth and is associated
with poor disease prognosis in epithelial ovarian cancer. J Histochem Cytochem 61:206–217
157. Pal S et al (2007) Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3
methylation in mantle cell lymphoma. EMBO J 26:3558–3569
158. Wang L et al (2008) Protein arginine methyltransferase 5 suppresses the transcription of the
RB family of tumor suppressors in leukemia and lymphoma cells. Mol Cell Biol
28:6262–6277
159. Chung J et al (2013) Protein arginine methyltransferase 5 (PRMT5) inhibition induces
lymphoma cell death through reactivation of the retinoblastoma tumor suppressor pathway
and Polycomb repressor complex 2 (PRC2) silencing. J Biol Chem 288:35534–35547
160. Nicholas C et al (2013) PRMT5 is upregulated in malignant and metastatic melanoma and
regulates expression of MITF and p27Kip1. PLoS One 8:e74710
161. Zhang H et al (1996) Codeletion of the genes for p16INK4, methylthioadenosine phosphorylase, interferon-α1, interferon-β1, and other 9p21 markers in human malignant cell lines.
Cancer Genet Cytogenet 86:22–28
162. Chan-Penebre E et al (2015) A selective inhibitor of PRMT5 with in vivo and in vitro potency
in MCL models. Nat Chem Biol 11:432–437
163. Duncan KW et al (2016) Structure and property guided design in the identification of PRMT5
tool compound EPZ015666. ACS Med Chem Lett 7:162–166
164. Tarighat SS et al (2016) The dual epigenetic role of PRMT5 in acute myeloid leukemia: gene
activation and repression via histone arginine methylation. Leukemia 30:789–799
165. Gerhart SV et al (2018) Activation of the p53-MDM4 regulatory axis defines the anti-tumour
response to PRMT5 inhibition through its role in regulating cellular splicing. Sci Rep 8:1–15
166. Bonday ZQ et al (2018) LLY-283, a potent and selective inhibitor of arginine
methyltransferase 5, PRMT5, with antitumor activity. ACS Med Chem Lett 9:612–617
167. SGC website: GSK591, a chemical probe for PRMT5. http://www.thesgc.org/chemicalprobes/GSK591. Accessed Jan 2019
168. Ji S et al (2016) Discovery of selective protein arginine methyltransferase 5 inhibitors and
biological evaluations. Chem Biol Drug Des:585–598
169. Waldmann T et al (2011) Methylation of H2AR29 is a novel repressive PRMT6 target.
Epigenetics Chromatin 4:11
170. Hyllus D et al (2007) PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4
trimethylation. Genes Dev 21:3369–3380
171. Guccione E et al (2007) Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL
complex are mutually exclusive. Nature 449:933–937
172. Sgarra R et al (2006) The AT-hook of the chromatin architectural transcription factor high
mobility group A1a is arginine-methylated by protein arginine methyltransferase 6. J Biol
Chem 281:3764–3772
173. El-Andaloussi N et al (2006) Arginine methylation regulates DNA polymerase β. Mol Cell
22:51–62
174. Boulanger M-C et al (2005) Methylation of tat by PRMT6 regulates human immunodeficiency
virus type 1 gene expression. J Virol 79:124–131
175. Singhroy DN et al (2013) Automethylation of protein arginine methyltransferase 6 (PRMT6)
regulates its stability and its anti-HIV-1 activity. Retrovirology 10:73
176. Vieira FQ et al (2014) Deregulated expression of selected histone methylases and
demethylases in prostate carcinoma. Endocr Relat Cancer 21:51–61
PRMT Inhibitors
195
31:1785–1797
154. Wei T-YW et al (2012) Protein arginine methyltransferase 5 is a potential oncoprotein that
upregulates G1 cyclins/cyclin-dependent kinases and the phosphoinositide 3-kinase/AKT
signaling cascade. Cancer Sci 103:1640–1650
155. Győrffy B et al (2013) Online survival analysis software to assess the prognostic value of
biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One 8:e82241
156. Bao X et al (2013) Overexpression of PRMT5 promotes tumor cell growth and is associated
with poor disease prognosis in epithelial ovarian cancer. J Histochem Cytochem 61:206–217
157. Pal S et al (2007) Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3
methylation in mantle cell lymphoma. EMBO J 26:3558–3569
158. Wang L et al (2008) Protein arginine methyltransferase 5 suppresses the transcription of the
RB family of tumor suppressors in leukemia and lymphoma cells. Mol Cell Biol
28:6262–6277
159. Chung J et al (2013) Protein arginine methyltransferase 5 (PRMT5) inhibition induces
lymphoma cell death through reactivation of the retinoblastoma tumor suppressor pathway
and Polycomb repressor complex 2 (PRC2) silencing. J Biol Chem 288:35534–35547
160. Nicholas C et al (2013) PRMT5 is upregulated in malignant and metastatic melanoma and
regulates expression of MITF and p27Kip1. PLoS One 8:e74710
161. Zhang H et al (1996) Codeletion of the genes for p16INK4, methylthioadenosine phosphorylase, interferon-α1, interferon-β1, and other 9p21 markers in human malignant cell lines.
Cancer Genet Cytogenet 86:22–28
162. Chan-Penebre E et al (2015) A selective inhibitor of PRMT5 with in vivo and in vitro potency
in MCL models. Nat Chem Biol 11:432–437
163. Duncan KW et al (2016) Structure and property guided design in the identification of PRMT5
tool compound EPZ015666. ACS Med Chem Lett 7:162–166
164. Tarighat SS et al (2016) The dual epigenetic role of PRMT5 in acute myeloid leukemia: gene
activation and repression via histone arginine methylation. Leukemia 30:789–799
165. Gerhart SV et al (2018) Activation of the p53-MDM4 regulatory axis defines the anti-tumour
response to PRMT5 inhibition through its role in regulating cellular splicing. Sci Rep 8:1–15
166. Bonday ZQ et al (2018) LLY-283, a potent and selective inhibitor of arginine
methyltransferase 5, PRMT5, with antitumor activity. ACS Med Chem Lett 9:612–617
167. SGC website: GSK591, a chemical probe for PRMT5. http://www.thesgc.org/chemicalprobes/GSK591. Accessed Jan 2019
168. Ji S et al (2016) Discovery of selective protein arginine methyltransferase 5 inhibitors and
biological evaluations. Chem Biol Drug Des:585–598
169. Waldmann T et al (2011) Methylation of H2AR29 is a novel repressive PRMT6 target.
Epigenetics Chromatin 4:11
170. Hyllus D et al (2007) PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4
trimethylation. Genes Dev 21:3369–3380
171. Guccione E et al (2007) Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL
complex are mutually exclusive. Nature 449:933–937
172. Sgarra R et al (2006) The AT-hook of the chromatin architectural transcription factor high
mobility group A1a is arginine-methylated by protein arginine methyltransferase 6. J Biol
Chem 281:3764–3772
173. El-Andaloussi N et al (2006) Arginine methylation regulates DNA polymerase β. Mol Cell
22:51–62
174. Boulanger M-C et al (2005) Methylation of tat by PRMT6 regulates human immunodeficiency
virus type 1 gene expression. J Virol 79:124–131
175. Singhroy DN et al (2013) Automethylation of protein arginine methyltransferase 6 (PRMT6)
regulates its stability and its anti-HIV-1 activity. Retrovirology 10:73
176. Vieira FQ et al (2014) Deregulated expression of selected histone methylases and
demethylases in prostate carcinoma. Endocr Relat Cancer 21:51–61
PRMT Inhibitors
195