Citrullination of glucokinase linked to autoimmune diabetes

Yang, Mei-Ling; S, Horstman; R, Gee; Guyer, Perrin; Tt, Lam; Kanyo, Jean; Al, Perdigoto; Speake, Cate; Cj, Greenbaum; Overbergh, Lutgart; Rg, Kibbey; Herold, KC; James, Eddie A.; Mj, Mamula

doi:10.1101/2021.04.28.441829

Cited by 3 publications

(3 citation statements)

References 55 publications

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“…A major role for PADs and citrullinated proteins has emerged in type 1 diabetes (Yang et al, 2021). Citrullination alters the enzyme kinetics of GK and suppresses GSIS (Yang et al, 2022).…”

Section: Other Ptmsmentioning

confidence: 99%

Regulation of insulin secretion by the post-translational modifications

Yang

Wei

Zhao

et al. 2023

Front. Cell Dev. Biol.

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Post-translational modification (PTM) has a significant impact on cellular signaling and function regulation. In pancreatic β cells, PTMs are involved in insulin secretion, cell development, and viability. The dysregulation of PTM in β cells is clinically associated with the development of diabetes mellitus. Here, we summarized current findings on major PTMs occurring in β cells and their roles in insulin secretion. Our work provides comprehensive insight into understanding the mechanisms of insulin secretion and potential therapeutic targets for diabetes from the perspective of protein PTMs.

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“…A major role for PADs and citrullinated proteins has emerged in type 1 diabetes (Yang et al, 2021). Citrullination alters the enzyme kinetics of GK and suppresses GSIS (Yang et al, 2022).…”

Section: Other Ptmsmentioning

confidence: 99%

Regulation of insulin secretion by the post-translational modifications

Yang

Wei

Zhao

et al. 2023

Front. Cell Dev. Biol.

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“…A study published last year showed that PADI1- and PADI3-mediated citrullination of the glycolytic enzyme pyruvate kinase M2 (PKM2) alters its binding to amino acids and promotes glycolysis in cancer cells [96]. A more recent study showed that citrullination of glukokinase leads to reduction of its catalytic activity and results in reduced insulin secretion in response to glucose stimulation [97]. These are, to the author's knowledge, the first reports that mechanistically link protein citrullination to the regulation of metabolic pathways.…”

Section: Molecular and Cellular Functions Regulated By Citrullination...mentioning

confidence: 99%

The virtues and vices of protein citrullination

Christophorou

2022

R. Soc. open sci.

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The post-translational modification of proteins expands the regulatory scope of the proteome far beyond what is achievable through genome regulation. The field of protein citrullination has seen significant progress in the last two decades. The small family of peptidylarginine deiminase (PADI or PAD) enzymes, which catalyse citrullination, have been implicated in virtually all facets of molecular and cell biology, from gene transcription and epigenetics to cell signalling and metabolism. We have learned about their association with a remarkable array of disease states and we are beginning to understand how they mediate normal physiological functions. However, while the biochemistry of PADI activation has been worked out in exquisite detail in vitro , we still lack a clear mechanistic understanding of the processes that regulate PADIs within cells, under physiological and pathophysiological conditions. This review summarizes and discusses the current knowledge, highlights some of the unanswered questions of immediate importance and gives a perspective on the outlook of the citrullination field.

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“…The PTMs were either citrullination and deamination of asparagine and glutamine residues, which are well‐known PTMs that occur in autoimmune diseases, such as rheumatoid arthritis (RA) and type 1 diabetes et al. [27, 30].…”

Section: Textmentioning

confidence: 99%

Development of a protein microarray for profiling circulating autoantibodies in human diseases

Ren

Wang

Wei

et al. 2022

Proteomics Clinical Apps

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Purpose To develop a robust microarray platform to detect thousands of serological autoantibodies (AAbs) simultaneously in different diseases. Experimental Design An AAbMap microarray was prepared by printing a total of 4032 purified His‐tagged human proteins and peptide probes on a chemically‐modified slide. The sensitivity, dynamic range, and the inter‐ and intra‐array reproducibility of the AAb microarray were then systematically tested and optimized. Finally, the large‐scale profiling of AAbs in the serum of patients with different human diseases using the AAbMap microarray was demonstrated. Results The dynamic range of antibody (Ab) detection was 2 to 3 orders of magnitude with the lowest limit of detection (LOD) of 68 pg/mL. The intra‐array (r) correlation of duplicate spots was 1.00, whereas the inter‐array correlations between different arrays and batches were 0.99 and 0.97 to 0.98, respectively. Notably, 132, 266, 171, and 84 AAbs were detected in pooled serum from healthy controls (HCs) or patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or lung cancer (LC), respectively. These AAbs included antibodies that target well‐known disease biomarkers, such as anti‐cyclic citrullinated peptide, anti‐ribonucleoprotein, and anti‐nucleosome. Conclusions and Clinical Relevance We developed a microarray platform to measure thousands of serological AAbs simultaneously with high sensitivity and reproducibility. The array can help study autoimmunity and complement genomics, proteomics, and metabolomics data for systematic investigations of human diseases.

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Citrullination of glucokinase linked to autoimmune diabetes

Cited by 3 publications

References 55 publications

Regulation of insulin secretion by the post-translational modifications

Regulation of insulin secretion by the post-translational modifications

The virtues and vices of protein citrullination

Development of a protein microarray for profiling circulating autoantibodies in human diseases

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