NDLI: Discovery of peptidylarginine deiminase-4 substrates by protein array: antagonistic citrullination and methylation of human ribosomal protein S2

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Molecular BioSystems Vol - 7 Issue - 6

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Discovery of peptidylarginine deiminase-4 substrates by protein array: antagonistic citrullination and methylation of human ribosomal protein S2

Content Provider	Royal Society of Chemistry (RSC)
Author	Guo, Qin Bedford, Mark T. Fast, Walter
Copyright Year	2011
Abstract	Peptidylarginine deiminase (PAD) catalyzes the posttranslational citrullination of selected proteins in a calcium dependent manner. The PAD4 isoform has been implicated in multiple sclerosis, rheumatoid arthritis, some types of cancer, and plays a role in gene regulation. However, the substrate selectivity of PAD4 is not well defined, nor is the impact of citrullination on many other pathways. Here, a high-density protein array is used as a primary screen to identify 40 previously unreported PAD4 substrates, 10 of which are selected and verified in a cell lysate-based secondary assay. One of the most prominent hits, human 40S ribosomal protein S2 (RPS2), is characterized in detail. PAD4 citrullinates the Arg–Gly repeat region of RPS2, which is also an established site for Arg methylation by protein arginine methyltransferase 3 (PRMT3). As in other systems, crosstalk is observed; citrullination and methylation modifications are found to be antagonistic to each other, suggesting a conserved posttranslational regulatory strategy. Both PAD4 and PRMT3 are found to co-sediment with the free 40S ribosomal subunit fraction from cell extracts. These findings are consistent with participation of citrullination in the regulation of RPS2 and ribosome assembly. This application of protein arrays to reveal new PAD4 substrates suggests a role for citrullination in a number of different cellular pathways.
Starting Page	2286
Ending Page	2295
Page Count	10
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	7
Issue Number	7
Journal	Molecular BioSystems
DOI	10.1039/c1mb05089c
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Citrullination Multiple sclerosis Crosstalk PRMT3 Eukaryotic small ribosomal subunit (40S) Ribosomal protein Protein Gene Arginine Rheumatoid arthritis Catalysis Calcium in biology Methylation Cancer
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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