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Biochemistry

PAD4

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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Thioredoxin Modulates Protein Arginine Deiminase 4 (Pad4)-Catalyzed Citrullination, Mitesh Nagar, Ronak Tilvawala, Paul R. Thompson Feb 2019

Thioredoxin Modulates Protein Arginine Deiminase 4 (Pad4)-Catalyzed Citrullination, Mitesh Nagar, Ronak Tilvawala, Paul R. Thompson

Open Access Articles

Protein citrullination is a post-translational modification catalyzed by the protein arginine deiminases (PADs). This modification plays a crucial role in the pathophysiology of numerous autoimmune disorders including RA. Recently, there has been a growing interest in investigating physiological regulators of PAD activity to understand the primary cause of the associated disorders. Apart from calcium, it is well-documented that a reducing environment activates the PADs. Although the concentration of thioredoxin (hTRX), an oxidoreductase that maintains the cellular reducing environment, is elevated in RA patients, its contribution toward RA progression or PAD activity has not been explored. Herein, we demonstrate that hTRX ...


Citrullination-Acetylation Interplay Guides E2f-1 Activity During The Inflammatory Response, Fatemeh Ghari, Anne-Marie Quirke, Shonagh Munro, Joanna Kawalkowska, Sarah Picaud, Joanna Mcgouran, Venkataraman Subramanian, Aaron Muth, Richard Williams, Benedikt Kessler, Paul R. Thompson, Panagis Fillipakopoulos, Stefan Knapp, Patrick J. Venables, Nicholas B. La Thangue Feb 2016

Citrullination-Acetylation Interplay Guides E2f-1 Activity During The Inflammatory Response, Fatemeh Ghari, Anne-Marie Quirke, Shonagh Munro, Joanna Kawalkowska, Sarah Picaud, Joanna Mcgouran, Venkataraman Subramanian, Aaron Muth, Richard Williams, Benedikt Kessler, Paul R. Thompson, Panagis Fillipakopoulos, Stefan Knapp, Patrick J. Venables, Nicholas B. La Thangue

Thompson Lab Publications

Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to ...


Activation Of Pad4 In Net Formation, Amanda S. Rohrbach, Daniel J. Slade, Paul R. Thompson, Kerri A. Mowen Nov 2012

Activation Of Pad4 In Net Formation, Amanda S. Rohrbach, Daniel J. Slade, Paul R. Thompson, Kerri A. Mowen

Thompson Lab Publications

Peptidylarginine deiminases, or PADs, convert arginine residues to the non-ribosomally encoded amino acid citrulline in a variety of protein substrates. PAD4 is expressed in granulocytes and is essential for the formation of neutrophil extracellular traps (NETs) via PAD4-mediated histone citrullination. Citrullination of histones is thought to promote NET formation by inducing chromatin decondensation and facilitating the expulsion of chromosomal DNA that is coated with antimicrobial molecules. Numerous stimuli have been reported to lead to PAD4 activation and NET formation. However, how this signaling process proceeds and how PAD4 becomes activated in cells is largely unknown. Herein, we describe the various ...