Autodeimination of protein arginine deiminase 4 alters protein-protein interactions but not activity.
Department of Biochemistry and Molecular Pharmacology
Enzyme Activation; HL-60 Cells; Histone Deacetylase 1; Histones; Humans; Hydrolases; Imines; *Protein Interaction Domains and Motifs; Protein Processing, Post-Translational; Protein-Arginine N-Methyltransferases; Recombinant Proteins; Repressor Proteins
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
The protein arginine deiminases (PAD), which catalyze the hydrolysis of peptidyl-arginine to form peptidyl-citrulline, play important roles in a variety of cell signaling pathways, including apoptosis, differentiation, and transcriptional regulation. In addition to these important cellular roles, PAD activity is dysregulated in multiple human diseases [e.g., rheumatoid arthritis (RA), cancer, and colitis], and significantly, PAD inhibition with Cl-amidine has been shown to reduce disease severity in the collagen-induced arthritis model of RA. Although these enzymes play important roles in human cell signaling and disease, the mechanisms that regulate PAD activity under both physiological and pathological conditions are poorly understood. One possible mechanism for regulating PAD activity is autodeimination, to which PAD4 has been shown by us and others to be subjected in vitro and in vivo. Herein, we demonstrate that PAD4 autodeimination does not alter the activity, substrate specificity, or calcium dependence of this isozyme. However, the results of these studies indicate a novel role for autodeimination in modulating the ability of PAD4 to interact with histone deacetylase 1 (HDAC1), citrullinated histone H3 (Cit H3), and protein arginine methyltransferase 1 (PRMT1).
DOI of Published Version
Biochemistry. 2011 May 17;50(19):3997-4010. doi: 10.1021/bi200309e. Epub 2011 Apr 20. Link to article on publisher's site
Slack JL, Jones LE, Bhatia MM, Thompson PR. (2011). Autodeimination of protein arginine deiminase 4 alters protein-protein interactions but not activity.. Thompson Lab Publications. https://doi.org/10.1021/bi200309e. Retrieved from https://escholarship.umassmed.edu/thompson/50