Protein arginine methylation of SERBP1 by protein arginine methyltransferase 1 affects cytoplasmic/nuclear distribution

2012 ◽  
Vol 113 (8) ◽  
pp. 2721-2728 ◽  
Author(s):  
Yu-Jen Lee ◽  
Wan-Yu Hsieh ◽  
Ling-Yun Chen ◽  
Chuan Li
Keyword(s):  
Arginine Methylation ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Nuclear Distribution ◽  
Protein Arginine Methylation ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

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 The Development of Tetrazole Derivatives as Protein Arginine Methyltransferase I (PRMT I) Inhibitors

2019 ◽  
Vol 20 (15) ◽  
pp. 3840 ◽  
Author(s):  
Sun ◽  
Wang ◽  
Yang ◽  
Zhu ◽  
Wu ◽  
...  
Keyword(s):  
Binding Free Energy ◽  
Arginine Methylation ◽  
Free Energy Calculations ◽  
Protein Arginine Methyltransferase ◽  
Dynamic Simulations ◽  
Arginine Methyltransferase ◽  
Diverse Range ◽  
Protein Arginine Methyltransferase 1 ◽  
Canonical Wnt ◽  
Tetrazole Derivatives

Protein arginine methyltransferase 1 (PRMT1) can catalyze protein arginine methylation by transferring the methyl group from S-adenosyl-L-methionine (SAM) to the guanidyl nitrogen atom of protein arginine, which influences a variety of biological processes. The dysregulation of PRMT1 is involved in a diverse range of diseases, including cancer. Therefore, there is an urgent need to develop novel and potent PRMT1 inhibitors. In the current manuscript, a series of 1-substituted 1H-tetrazole derivatives were designed and synthesized by targeting at the substrate arginine-binding site on PRMT1, and five compounds demonstrated significant inhibitory effects against PRMT1. The most potent PRMT1 inhibitor, compound 9a, displayed non-competitive pattern with respect to either SAM or substrate arginine, and showed the strong selectivity to PRMT1 compared to PRMT5, which belongs to the type II PRMT family. It was observed that the compound 9a inhibited the functions of PRMT1 and relative factors within this pathway, and down-regulated the canonical Wnt/β-catenin signaling pathway. The binding of compound 9a to PRMT1 was carefully analyzed by using molecular dynamic simulations and binding free energy calculations. These studies demonstrate that 9a was a potent PRMT1 inhibitor, which could be used as lead compound for further drug discovery.

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
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