Journal article

N-Terminomics/TAILS Profiling of Proteases and Their Substrates in Ulcerative Colitis

MH Gordon, A Anowai, D Young, N Das, RI Campden, H Sekhon, Z Myers, B Mainoli, S Chopra, PS Thuy-Boun, J Kizhakkedathu, G Bindra, HB Jijon, S Heitman, R Yates, DW Wolan, LE Edgington-Mitchell, WK MacNaughton, A Dufour

ACS Chemical Biology | AMER CHEMICAL SOC | Published : 2019

Abstract

Dysregulated protease activity is often implicated in the initiation of inflammation and immune cell recruitment in gastrointestinal inflammatory diseases. Using N-terminomics/TAILS (terminal amine isotopic labeling of substrates), we compared proteases, along with their substrates and inhibitors, between colonic mucosal biopsies of healthy patients and those with ulcerative colitis (UC). Among the 1642 N-termini enriched using TAILS, increased endogenous processing of proteins was identified in UC compared to healthy patients. Changes in the reactome pathways for proteins associated with metabolism, adherens junction proteins (E-cadherin, liver-intestinal cadherin, catenin alpha-1, and cate..

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University of Melbourne Researchers

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Funding Acknowledgements

The authors thank L. Brechenmacher and the Southern Alberta Mass Spectrometry (SAMS) core facility for assistance with the LC-MS/MS analysis and the Intestinal Inflammation Tissue Bank (IITB) at the University of Calgary for collection of human tissue and patient characteristics. We thank the Natural Sciences and Engineering Research Council (NSERC) and Crohn's and Colitis Canada for funding. L.E.E.-M. was supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia (NHMRC, GNT1091636), a Grimwade Fellowship from the Russell and Mab Grimwade Miegunyah Fund at The University of Melbourne, and a DECRA Fellowship from the Australian Research Council (ARC, DE180100418).