title: Chemical Proteomic Platform To Identify Citrullinated Proteins.
abstract: 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.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Lewallen
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Bicker
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Subramanian
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Clancy
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Slade
authors.affiliation: Department of Chemistry, Boston College , Chestnut Hill, Massachusetts 02467, United States.
authors.forename: Julianne
authors.initials: J
authors.lastname: Martell
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Dreyton
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine , Stanford, California 94305, United States.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
authors.affiliation: Department of Chemistry, Boston College , Chestnut Hill, Massachusetts 02467, United States.
authors.forename: Eranthie
authors.initials: E
authors.lastname: Weerapana
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Thompson
mesh_terms: D002956:Citrulline / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006657:Histones / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D011506:Proteins / Q000032:analysis* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D006657:Histones; D011506:Proteins; D002956:Citrulline