Chemical Proteomic Platform To Identify Citrullinated Proteins

Anti-citrullinated protein antibodies
(ACPAs) are a hallmark of
rheumatoid arthritis (RA) and are routinely used for disease diagnosis.
Protein citrullination is also increased in cancer and other autoimmune
disorders, suggesting that citrullinated proteins may serve as biomarkers
for diseases beyond RA. To identify these citrullinated proteins,
we developed biotin-conjugated phenylglyoxal (biotin-PG). Using this
probe and our platform technology, we identified >50 intracellular
citrullinated proteins. More than 20 of these are involved in RNA
splicing, suggesting, for the first time, that citrullination modulates
RNA biology. Overall, this chemical proteomic platform will play a
key role in furthering our understanding of protein citrullination
in rheumatoid arthritis and potentially a wider spectrum of inflammatory
diseases.