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Chemical Proteomic Platform To Identify Citrullinated Proteins
Daniel M Lewallen, Kevin L Bicker, Venkataraman Subramanian1
1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.
Researchers identified over 50 intracellular citrullinated proteins, including more than 20 involved in RNA splicing. This discovery suggests protein citrullination impacts RNA biology and may serve as a biomarker for rheumatoid arthritis and other inflammatory diseases.
Area of Science:
- Biochemistry
- Proteomics
- Molecular Biology
Background:
- Anti-citrullinated protein antibodies (ACPAs) are key diagnostic markers for rheumatoid arthritis (RA).
- Elevated protein citrullination is observed in cancer and other autoimmune diseases, indicating potential broader biomarker applications.
- Understanding the full scope of protein citrullination is crucial for disease diagnostics and therapeutics.
Purpose of the Study:
- To identify novel intracellular citrullinated proteins beyond those associated with RA.
- To investigate the role of protein citrullination in cellular processes, particularly RNA biology.
- To establish a chemical proteomic platform for studying protein citrullination.
Main Methods:
- Development of a biotin-conjugated phenylglyoxal (biotin-PG) probe for detecting citrullinated proteins.
- Application of a chemical proteomic platform utilizing the biotin-PG probe.
- Mass spectrometry-based identification of intracellular citrullinated proteins.
Main Results:
- >50 intracellular citrullinated proteins were identified.
- Over 20 identified proteins are involved in RNA splicing.
- This study reveals a novel link between protein citrullination and RNA biology.
Conclusions:
- Protein citrullination plays a significant role in modulating RNA biology.
- The identified citrullinated proteins represent potential biomarkers for RA and other inflammatory diseases.
- The developed chemical proteomic platform offers a valuable tool for future research in protein citrullination and related diseases.
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