更新于：2024-09-19

PRMT9

更新于：2024-09-19

基本信息

别名

FLJ46629、PRMT10、PRMT9

+ [4]

简介

Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA). Specifically mediates the symmetrical dimethylation of SF3B2. Involved in the regulation of alternative splicing of pre-mRNA (PubMed:25737013, PubMed:25979344).

关联

项与 PRMT9 相关的药物

EML-1219

靶点

PRMT9

作用机制

PRMT9调节剂

在研机构

University of Salerno

原研机构

University of Salerno

在研适应症-

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

EML-734

靶点

PRMT9

作用机制

PRMT9调节剂

在研机构

University of Salerno

原研机构

University of Salerno

在研适应症-

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PRMT9 相关的临床结果

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100 项与 PRMT9 相关的转化医学

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0 项与 PRMT9 相关的专利（医药）

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项与 PRMT9 相关的文献（医药）

2023-10-12·Journal of medicinal chemistry1区 · 医学

Identification of a Protein Arginine Methyltransferase 7 (PRMT7)/Protein Arginine Methyltransferase 9 (PRMT9) Inhibitor.

1区 · 医学

Article

作者: Sarno, Giuliana ; Shen, Lei ; Wang, Zhihao ; Iannelli, Giulia ; Feoli, Alessandra ; Monti, Maria Chiara ; Viviano, Monica ; Hadjikyriacou, Andrea ; Clarke, Steven G ; Cosconati, Sandro ; Yang, Yanzhong ; Cipriano, Alessandra ; Castellano, Sabrina ; Morretta, Elva ; Safaeipour, Cyrus ; Milite, Ciro ; Sbardella, Gianluca ; Lowe, Troy L

Less studied than the other protein arginine methyltransferase isoforms, PRMT7 and PRMT9 have recently been identified as important therapeutic targets. Yet, most of their biological roles and functions are still to be defined, as well as the structural requirements that could drive the identification of selective modulators of their activity. We recently described the structural requirements that led to the identification of potent and selective PRMT4 inhibitors spanning both the substrate and the cosubstrate pockets. The reanalysis of the data suggested a PRMT7 preferential binding for shorter derivatives and prompted us to extend these structural studies to PRMT9. Here, we report the identification of the first potent PRMT7/9 inhibitor and its binding mode to the two PRMT enzymes. Label-free quantification mass spectrometry confirmed significant inhibition of PRMT activity in cells. We also report the setup of an effective AlphaLISA assay to screen small molecule inhibitors of PRMT9.

2023-06-01·Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Histone H4K20 monomethylation enables recombinant nucleosome methylation by PRMT1 in vitro

Article

作者: Thibault, Pierre ; Homsi, Charles ; Bonneil, Eric ; Verreault, Alain ; Vedadi, Masoud ; Li, Alice Shi Ming

Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups to specific arginine residues of histones and nonhistone proteins. There are nine members in the PRMT family (PRMT1 to PRMT9), and PRMT1 is a dominant member catalyzing majority of arginine methylation in the cell. However, none of the PRMTs is active with recombinant nucleosome as substrate in vitro. Here, we report the discovery of the first in class novel crosstalk between histone H4 lysine 20 (H4K20) monomethylation on nucleosome by SETD8 and histone H4 arginine 3 (H4R3) methylation by PRMT1 in vitro. Full kinetic characterization and mass spectrometry analysis indicated that PRMT1 is only active with recombinant nucleosomes monomethylated at H4K20 by SETD8. These data suggests that the level of activity of PRMT1 could potentially be regulated selectively by SETD8 in various pathways, providing a new approach for discovery of selective regulators of PRMT1 activity.

2023-03-01·Histology and histopathology

Elucidating the role of PRMTs in prostate cancer using open access databases and a patient cohort dataset.

Article

作者: Melachrinou, Maria ; Megalooikonomou, Vasileios ; Bravou, Vasiliki ; Grypari, Ioanna Maria ; Pappa, Ioanna ; Zolota, Vasiliki ; Papastergiou, Thomas ; Tzelepi, Vasiliki

Protein arginine methylation is an understudied epigenetic mechanism catalyzed by enzymes known as Protein Methyltransferases of Arginine (PRMTs), while the opposite reaction is performed by Jumonji domain- containing protein 6 (JMJD6). There is increasing evidence that PRMTs are deregulated in prostate cancer (PCa). In this study, the expression of two PRMT members, PRMT2 and PRMT7 as well as JMJD6, a demethylase, was analyzed in PCa. Initially, we retrieved data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) database to explore the differential expression of various PRMT family members in patients with PCa and then applied immunohistochemistry in a patient cohort across the spectrum of PCa, including non-neoplastic prostate tissue and lymph node metastatic foci. The results from the TCGA analysis revealed that PRMT7, PRMT6 and PRMT3 expression increased while PRMT2, PRMT9 and JMJD6 levels decreased in the tumor compared to non-neoplastic prostate. Results from the GEO datasets were similar, albeit not identical with the TCGA results, with PRMT7 and PRMT3 being upregulated and PRMT2 and JMJD6 being downregulated in the tumor compared to non-neoplastic tissue in some of them. In addition, PRMT7 levels decreased with stage and grade progression in the TCGA analysis. In the patient cohort, both PRMTs and JMJD6 were overexpressed in PCa compared to non-neoplastic tissue, and nuclear PRMT2 and JMJD6 were upregulated in lymph node metastasis, too. PRMT7 and JMJD6 expression were upregulated with the progression of stage and JMJD6 was also increased with the elevation of grade. After androgen ablation therapy, nuclear expression of PRMT7 and JMJD6 were elevated compared to untreated tumors. PRMT2, PRMT7 and JMD6 were also correlated with markers of EMT and cell cycle regulators. Finally, our findings indicate that PRMTs and JMJD6 are involved in prostate cancer progression and revealed a potential interplay of PRMTs with EMT mediators, underscoring the need for therapeutic targeting of arginine methylation in prostate cancer.