Chemical Proteomic Platform To Identify Citrullinated Proteins.
Chemical Proteomic Platform To Identify Citrullinated Proteins.
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DOI：
10.1021/acschembio.5b00438
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发表时间：
2015-11-20
影响因子：
4
通讯作者：
Thompson PR
中科院分区：
文献类型：
--
作者：
Lewallen DM;Bicker KL;Subramanian V;Clancy KW;Slade DJ;Martell J;Dreyton CJ;Sokolove J;Weerapana E;Thompson PR
抗瓜氨酸蛋白抗体（ACPA）是类风湿性关节炎（RA）的标志，通常用于疾病诊断。瓜氨酸蛋白在癌症和其他自身免疫性疾病中也会增加，这表明瓜氨酸化蛋白可以作为RA以外疾病的生物标志物。为了鉴定这些瓜氨酸化蛋白，我们开发了生物素缀合的苯乙二醛（生物素-PG）。使用这种探针和我们的平台技术，我们鉴定了超过50种细胞内瓜氨酸化蛋白。其中超过20种参与RNA剪接，这首次表明瓜氨酸调节RNA生物学。总的来说，这个化学蛋白质组学平台将在促进我们对瓜氨酸蛋白在类风湿性关节炎和潜在的更广泛的炎症性疾病中的理解方面发挥关键作用。
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.