Down-regulation of protein arginine methyltransferase 1 (PRMT1) gene expression in renal cell carcinomas

2016 ◽  
Author(s):  
Jelena Vještica
Keyword(s):  
Gene Expression ◽  
Renal Cell ◽  
Renal Cell Carcinomas ◽  
Down Regulation ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

scholarly journals Protein Arginine Methyltransferase 1 (PRMT1) Selective Inhibitor, TC-E 5003, Has Anti-Inflammatory Properties in TLR4 Signaling

2020 ◽  
Vol 21 (9) ◽  
pp. 3058
Author(s):  
Eunji Kim ◽  
Jiwon Jang ◽  
Jae Gwang Park ◽  
Kyung-Hee Kim ◽  
Keejung Yoon ◽  
...  
Keyword(s):  
Gene Expression ◽  
No Production ◽  
Type I ◽  
Rt Pcr ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Anti Inflammatory ◽  
Protein Arginine Methyltransferase 1 ◽  
Factor C ◽  
Methyltransferase 1

Protein arginine methyltransferase 1 (PRMT1) is the most predominant PRMT and is type I, meaning it generates monomethylarginine and asymmetric dimethylarginine. PRMT1 has functions in oxidative stress, inflammation and cancers, and modulates diverse diseases; consequently, numerous trials to develop PRMT1 inhibitors have been attempted. One selective PRMT1 inhibitor is N,N′-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide), also named TC-E 5003 (TC-E). In this study, we investigated whether TC-E regulated inflammatory responses. Nitric oxide (NO) production was evaluated by the Griess assay and the inflammatory gene expression was determined by conducting RT-PCR. Western blot analyzing was carried out for inflammatory signaling exploration. TC-E dramatically reduced lipopolysaccharide (LPS)-induced NO production and the expression of inflammatory genes (inducible NO synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and interleukin (IL)-6) as determined using RT-PCR. TC-E downregulated the nuclear translocation of the nuclear factor (NF)-κB subunits p65 and p50 and the activator protein (AP)-1 transcriptional factor c-Jun. Additionally, TC-E directly regulated c-Jun gene expression following LPS treatment. In NF-κB signaling, the activation of IκBα and Src was attenuated by TC-E. Taken together, these data show that TC-E modulates the lipopolysaccharide (LPS)-induced AP-1 and NF-κB signaling pathways and could possibly be further developed as an anti-inflammatory compound.

scholarly journals Cytoplasmic sequestration of FUS/TLS associated with ALS alters histone marks through loss of nuclear protein arginine methyltransferase 1

2014 ◽  
Vol 24 (3) ◽  
pp. 773-786 ◽  
Author(s):  
Michael Tibshirani ◽  
Miranda L. Tradewell ◽  
Katie R. Mattina ◽  
Sandra Minotti ◽  
Wencheng Yang ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Histone Marks ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

Abstract 457: Protein Arginine Methyltransferase-1 is Required for Epicardial Epithelial-to-Mesenchymal Transition

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Olan Jackson-Weaver ◽  
Jian Wu ◽  
Yongchao Gou ◽  
Shihong Shi ◽  
Henry Sucov ◽  
...  
Keyword(s):  
Cell Types ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
P53 Expression ◽  
Epicardial Cells ◽  
Epicardial Cell ◽  
Protein Arginine Methyltransferase 1 ◽  
E Cadherin ◽  
Methyltransferase 1

Rationale: Epicardial epithelial-to-mesenchymal trasition (EMT) is a vital process in embryonic heart development. During EMT, epicardial cells acquire migratory and invasive properties, and differentiate into new cell types, including cardiac fibroblasts and coronary smooth muscle cells. EMT is characterized by an increase in mesenchymal proteins such as Slug and Fibronectin, and a decrease in cell-junction proteins such as E-Cadherin, and is dependent on TGF-β signaling. We have recently demonstrated that protein arginine methyltransferase-1 (PRMT1) is necessary for TGF-β family signaling and EMT in non-epicardial cell types. Objective: To determine the role of PRMT1 in epicardial EMT. Methods and Results: We investigated the role of PRMT1 in epicardial EMT in mouse epicardial cells. PRMT1 siRNA prevented the increase in Slug and Fibronectin and the decrease in E-Cadherin in TGF-β treatment-induced EMT of mouse epicardial cell line MEC1. PRMT1 siRNA also reduced the migration and invasion of MEC1 cells. These results demonstrate that PRMT1 is required for epicardial EMT. In WT1-Cre ERT ;ROSA-YFP fl/fl mouse embryos, PRMT1 siRNA reduced epicardial EMT in a thorax culture model. Among the key transcription factors that regulate the EMT program, Slug, but not Snail, is specifically regulated by PRMT1. We further identified that PRMT1 siRNA also increased the expression of p53, a key regulator of the Slug degradation pathway. PRMT1 siRNA increases p53 expression by decreasing p53 degradation, and shifted p53 localization to the cytoplasm. In vitro methylation assays further demonstrated that PRMT1 methylates p53. Knockdown of p53 increased Slug levels and enhanced EMT, establishing p53 as a regulator of epicardial EMT through controlling Slug expression. Conclusions: The PRMT1-p53-Slug pathway is necessary for epicardial EMT in cultured MEC1 cells as well as in the epicardium ex vivo .

scholarly journals Kinetic Mechanism of Protein Arginine Methyltransferase 1†

Biochemistry ◽  
2008 ◽  
Vol 47 (39) ◽  
pp. 10420-10427 ◽  
Author(s):  
Obiamaka Obianyo ◽  
Tanesha C. Osborne ◽  
Paul R. Thompson
Keyword(s):  
Kinetic Mechanism ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

scholarly journals The polymorphism rs975484 in the protein arginine methyltransferase 1 gene modulates expression of immune checkpoint genes in hepatocellular carcinoma

2020 ◽  
Vol 295 (20) ◽  
pp. 7126-7137 ◽  
Author(s):  
Michael Schonfeld ◽  
Jie Zhao ◽  
Amberly Komatz ◽  
Steven A. Weinman ◽  
Irina Tikhanovich
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoints ◽  
Luciferase Reporter ◽  
Antibody Treatment ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Protein Arginine Methyltransferase 1 ◽  
Checkpoint Genes ◽  
Methyltransferase 1

Protein arginine methyltransferase 1 (PRMT1) is a key regulator of hepatic immune responses. Recently, we reported that PRMT1 regulates the tumor immune response in hepatocellular carcinoma (HCC). Here we found that PRMT1 expression in human HCC correlates with that of programmed cell death 1 ligand 1 (PD-L1), PD-L2, and other checkpoint genes. PRMT1 deletion in mice reduced PD-L1 and PD-L2 expression in tumors and reduced the efficiency of PD-1 antibody treatment in a diethylnitrosamine-induced HCC mouse model, suggesting that PRMT1 regulates the hepatic immune checkpoint. Mice had reduced PD-L1 and PD-L2 expression when PRMT1 was specifically deleted in tumor cells or macrophages, but PRMT1 deletion in dendritic cells did not alter PD-L1 and PD-L2 expression. rs975484 is a common polymorphism in the human PRMT1 gene promoter, and we found that it alters PRMT1 expression in blood monocytes and tumor-associated macrophages in human HCC. PRMT1 expression was higher in individuals with a GG genotype than in individuals with a CC genotype, and heterozygous carriers had intermediate expression. Luciferase reporter assays indicated that this differential expression is due to an extra C/EBPβ-binding site in the PRMT1 promoter of individuals carrying the minor G allele. The rs975484 genotype also correlated with PRMT1 target expression in HCC. Individuals with the GG genotype had significantly higher levels of the PRMT1 targets PD-L1, PD-L2, and VISTA than those with the CC genotype. We conclude that PRMT1 critically controls immune checkpoints in mice and humans and that the PRMT1 polymorphism rs975484 affects checkpoint gene expression in HCC.

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