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 language | English |
|---|---|
| Pages (from-to) | 31766-31773 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 278 |
| Issue number | 34 |
| DOIs | |
| Publication status | Published - Aug 22 2003 |
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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 journal › Article
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TY - JOUR
T1 - Proteomics identification of acyl-acceptor and acyl-donor substrates for transglutaminase in a human intestinal epithelial cell line. Implications for celiac disease
AU - Orrù, Stefania
AU - Caputo, Ivana
AU - D'Amato, Alfonsina
AU - Ruoppololl, Margherita
AU - Esposito, Carla
PY - 2003/8/22
Y1 - 2003/8/22
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0041355325&partnerID=8YFLogxK
U2 - 10.1074/jbc.M305080200
DO - 10.1074/jbc.M305080200
M3 - Article
C2 - 12799366
AN - SCOPUS:0041355325
VL - 278
SP - 31766
EP - 31773
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 34
ER -