Posttranslational modifications as therapeutic targets for intestinal disorders. (March 2021)

• Record Type: Journal Article
• Authors: Choo, Jieun; Heo, Gwangbeom; Pothoulakis, Charalabos; Im, Eunok
• Is Part Of: Pharmacological research. Volume 165(2021)
• Publication Date: 2021-03
• Subjects: AICAR 5-aminoimidazole-4-carboxamide ribonucleoside -- AMPK 5′ adenosine monophosphate-activated protein kinase -- BDNF brain-derived neurotrophic factor -- CACC colitis-associated colon cancer -- CD Crohn's disease -- CHI3L1 chitinase 3-like 1 -- COP9 constitutive photomorphogenesis 9 -- CRC colorectal cancer -- CSN6 constitutive photomorphogenesis 9 signalosome 6 -- DSS dextran sulfate sodium -- DUBA deubiquitinating enzyme A -- EGFR epidermal growth factor receptor -- ERK extracellular signal-regulated protein kinase -- GPCR G protein-coupled receptor -- IBD inflammatory bowel disease -- IBS irritable bowel syndrome -- IBS-C constipation-predominant IBS -- IBS-D diarrhea-predominant IBS -- IBS-M IBS with a mixed stool pattern -- IBS-PI post-infectious IBS -- IEC intestinal epithelial cell -- IFN interferon -- Ig immunoglobulin -- IκB inhibitor of NF-κB -- IKK IκB kinase -- IL interleukin -- IL-1Ra IL-1 receptor antagonist -- JAK janus kinase -- JNK c-Jun NH2-terminal kinase -- LPMC lamina propria mononuclear cell -- LPS lipopolysaccharide -- MAPK mitogen-activated protein kinase -- MDM2 mouse double minute 2 homolog -- MLC myosin light chain -- MLCK myosin light chain kinase -- MOR μ opioid receptor -- NF-κB nuclear factor-kappa B -- NLRP3 nucleotide-binding domain- leucine-rich repeat- and pyrin domain-containing receptor 3 -- NLS nuclear localization sequence -- NMDAR N-methyl-d-aspartate receptor -- NOD2 nucleotide-binding oligomerization domain-containing protein 2 -- PAR2 protease-activated receptor 2 -- PI3K phosphatidylinositol-45-bisphosphate 3-kinase -- PKB protein kinase B -- PPARγ peroxisome proliferator-activated receptor gamma -- PTM posttranslational modification -- RNF6 ring finger protein 6 -- RORγt retinoic acid related orphan nuclear receptor gamma t -- STAT3 signal transducer and activator of transcription 3 -- TG2 tissue transglutaminase -- TGF transforming growth factor -- TLE3 transducin-like enhancer of split 3 -- TNBS 24, 6-trinitrobenzenesulfonic acid -- TNF tumor necrosis factor -- TRAF6 tumor necrosis factor receptor associated factor 6 -- UC ulcerative colitis -- USP7 ubiquitin-specific-processing protease 7 -- VEGF vascular endothelial growth factor -- ZO-1 zonula occludens-1; 2, 4, 6-trinitrobenzenesulfonic acid (PubChem CID: 11045) -- SP600125 (PubChem CID: 8515) -- XG-102 (PubChem CID: 90479374) -- PD98059 (PubChem CID: 4713) -- SB203580 (PubChem CID: 176155) -- FR167653 (PubChem CID: 135484078) -- Mangiferin (PubChem CID: 5281647) -- AS605240 (PubChem CID: 5289247) -- Pyrrolidine dithiocarbamate (PubChem CID: 65351) -- DAMGO (PubChem CID: 5462471); Inflammatory bowel disease -- Irritable bowel syndrome -- Celiac disease -- Colorectal cancer -- Cytokines -- NF-κB; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105412
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: A variety of biological processes are regulated by posttranslational modifications. Posttranslational modifications including phosphorylation, ubiquitination, glycosylation, and proteolytic cleavage, control diverse physiological functions in the gastrointestinal tract. Therefore, a better understanding of their implications in intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, celiac disease, and colorectal cancer would provide a basis for the identification of novel biomarkers as well as attractive therapeutic targets. Posttranslational modifications can be common denominators, as well as distinct biomarkers, characterizing pathological differences of various intestinal diseases. This review provides experimental evidence that identifies changes in posttranslational modifications from patient samples, primary cells, or cell lines in intestinal disorders, and a summary of carefully selected information on the use of pharmacological modulators of protein modifications as therapeutic options.