Histone Citrullination by Protein Arginine Deiminase: Is Arginine Methylation a Green Light or a Roadblock?

2006 ◽  
Vol 1 (7) ◽  
pp. 433-441 ◽  
Author(s):  
Paul R. Thompson ◽  
Walter Fast
Keyword(s):  
Green Light ◽  
Arginine Methylation ◽  
Arginine Deiminase ◽  
Protein Arginine Deiminase ◽  
Histone Citrullination

scholarly journals Protein Arginine Deiminase 4 Antagonizes Methylglyoxal-induced Histone Glycation

2019 ◽  
Author(s):  
Qingfei Zheng ◽  
Adewola Osunsade ◽  
Yael David
Keyword(s):  
Metabolic Stress ◽  
Arginine Methylation ◽  
Arginine Deiminase ◽  
Side Chains ◽  
Epigenetic Landscape ◽  
Chromatin Architecture ◽  
Protein Arginine Deiminase ◽  
Arginine Residues ◽  
Histone Citrullination ◽  
Oxygen Substitution

AbstractProtein arginine deiminase 4 (PAD4) facilitates the post-translational citrullination of the core histones H3 and H4. While the precise epigenetic function of this modification has not been resolved, it was shown to associate with general chromatin decompaction and to compete with arginine methylation. Recently, we showed that histones are subjected to methylglyoxal (MGO)-induced glycation on nucleophilic side chains, particularly arginines, under metabolic stress conditions. These non-enzymatic adducts change chromatin architecture and the epigenetic landscape by competing with enzymatic modifications. Here we report that PAD4 antagonizes histone MGO-glycation by protecting the reactive sites with oxygen substitution, as well as by converting already-glycated arginine residues into citrulline. Moreover, we show that similar to the deglycase DJ-1, PAD4 is overexpressed and histone citrullination is upregulated in breast cancer tumors, suggesting an additional mechanistic link to PAD4’s oncogenic properties.SignificanceMetabolic syndromes and diabetes increase the risk for certain diseases such as cancer. However, the mechanism behind this correlation is poorly understood. Methylglyoxal (MGO), a reactive dicarbonyl sugar metabolite found in cells under metabolic stress, can non-enzymatically modify arginine and lysine residues in histone proteins, making it a new epigenetic marker linking metabolism and disease. Histone MGO-glycation induces changes in chromatin architecture and the epigenetic landscape, and abrogates gene transcription. In this study, we found that protein arginine deiminase 4 (PAD4) exhibits dual functions to antagonize histone MGO-glycation: removing glycation adducts from arginines and converting the unmodified side chains into citrulline, which protects them from undergoing glycation. This unprecedented biochemical mechanism demonstrates a potential function of PAD4 in cancer cells.

scholarly journals Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides

2021 ◽  
Vol 92 ◽  
pp. 107487
Author(s):  
Izzuddin Ahmad Nadzirin ◽  
Adam Leow Thean Chor ◽  
Abu Bakar Salleh ◽  
Mohd Basyaruddin Abdul Rahman ◽  
Bimo A. Tejo
Keyword(s):  
Rational Design ◽  
Arginine Deiminase ◽  
Protein Arginine Deiminase

scholarly journals Autodeimination of Protein Arginine Deiminase 4 Alters Protein–Protein Interactions but Not Activity

Biochemistry ◽  
2011 ◽  
Vol 50 (19) ◽  
pp. 3997-4010 ◽  
Author(s):  
Jessica L. Slack ◽  
Larry E. Jones ◽  
Monica M. Bhatia ◽  
Paul R. Thompson
Keyword(s):  
Protein Interactions ◽  
Arginine Deiminase ◽  
Protein Protein Interactions ◽  
Protein Arginine Deiminase

scholarly journals ATP Induces Protein Arginine Deiminase 2-Dependent Citrullination in Mast Cells through the P2X7 Purinergic Receptor

2012 ◽  
Vol 189 (8) ◽  
pp. 4112-4122 ◽  
Author(s):  
Sanja Arandjelovic ◽  
Katherine R. McKenney ◽  
Sunamita S. Leming ◽  
Kerri A. Mowen
Keyword(s):  
Mast Cells ◽  
Purinergic Receptor ◽  
Arginine Deiminase ◽  
Protein Arginine Deiminase

Evaluation of protein arginine deiminase-4 inhibitor in TNBS- induced colitis in mice

2020 ◽  
Vol 84 ◽  
pp. 106583
Author(s):  
Tingting Zhang ◽  
Yinliu Mei ◽  
Wanfa Dong ◽  
Jingxun Wang ◽  
Fengjie Huang ◽  
...  
Keyword(s):  
Arginine Deiminase ◽  
Protein Arginine Deiminase

scholarly journals Synthesis and Biological Evaluation of an Indazole-Based Selective Protein Arginine Deiminase 4 (PAD4) Inhibitor

2018 ◽  
Vol 9 (10) ◽  
pp. 1013-1018 ◽  
Author(s):  
Caroline Chandra Tjin ◽  
Rebecca F. Wissner ◽  
Haya Jamali ◽  
Alanna Schepartz ◽  
Jonathan A. Ellman
Keyword(s):  
Biological Evaluation ◽  
Arginine Deiminase ◽  
Protein Arginine Deiminase ◽  
Synthesis And Biological Evaluation
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