Proteomics identification of acyl-acceptor and acyl-donor substrates for transglutaminase in a human intestinal epithelial cell line. Implications for celiac disease

Stefania Orrù, Ivana Caputo, Alfonsina D'Amato, Margherita Ruoppololl, Carla Esposito

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Transglutaminase (TG)-catalyzed cross-linking of both intracellular and extracellular proteins is an important biochemical event. However, increased concentrations of cross-linked proteins have been observed in many disorders. Moreover, TG-catalyzed modification of proteins might generate new self-antigens responsible for the autoimmune response, as in celiac disease. The identification of available substrates may offer an understanding of how the TG-catalyzed post-translational modification has an impact on physiology and disease. We used a proteomic approach to identify TG-modified protein targets in human intestinal epithelial cells to determine the extent to which transglutaminase specifically contributes to celiac disease. Two probes were used for endogenous TG activity: 5-(biotinamido)pentylamine, which represents the acyl-acceptor, and a biotinylated glutamine-containing peptide, which represents the acyl-donor. This approach identified >25 proteins, which range from 30,000 to 300,000 Daltons and can serve as acyl-acceptor and/or acyl-donor for transglutaminase. Some of them were known transglutaminase substrates, whereas others had not been previously identified. These targets include proteins involved in cytoskeletal network organization, folding of proteins, transport processes, and miscellaneous metabolic functions.

Original languageEnglish
Pages (from-to)31766-31773
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number34
DOIs
Publication statusPublished - Aug 22 2003

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Transglutaminases
Celiac Disease
Proteomics
Epithelial Cells
Cell Line
Substrates
Proteins
Autoantigens
Protein Transport
Post Translational Protein Processing
Glutamine
Autoimmunity
Physiology
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Proteomics identification of acyl-acceptor and acyl-donor substrates for transglutaminase in a human intestinal epithelial cell line. Implications for celiac disease. / Orrù, Stefania; Caputo, Ivana; D'Amato, Alfonsina; Ruoppololl, Margherita; Esposito, Carla.

In: Journal of Biological Chemistry, Vol. 278, No. 34, 22.08.2003, p. 31766-31773.

Research output: Contribution to journalArticle

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