New cellular pathway in inflammatory bowel disease (IBD) that provides a novel lead for therapeutic intervention for IBD
05 Jul 2017
By Dr C. V. Srikanth, Intemediate Fellow 2011
Regional Center for Biotechnology, Faridabad
Modern ways of living have led to a sudden rise in abnormal immune function which results in various auto-immune diseases. Inflammatory bowel disease (IBD) is one such disorder of gastrointestinal (GI) tract involving chronic abnormal immune activation. Symptoms include recurrent diarrhea, abdominal cramps, weight loss, fatigue and fever and a terribly compromised ‘quality of life’ in patients.
Several molecular pathways in cells have been tested for therapeutic interventions but none have been found to be fully effective. In our recently published study in Open Biology we have investigated possible role for SUMOylation in IBD. SUMOylation is an inherent post-translational modification pathway involving various enzymes that alter the structure of proteins which consequently regulates their location inside the cell. Defects in the SUMOylation pathway have been shown to contribute to various cancers, protein aggregating disorders, such as Huntington's, Alzheimer's, Parkinson's diseases and, some developmental disorders.
In our published study that employed mice model and human patient samples, we demonstrate existence of an aberrant SUMOylation pathway which caused a global molecular signaling alteration including a SUMOylation-dependent malfunctioning of master signaling regulator Akt1, a key protein in inflammatory pathways. These findings, the first of its kind in IBD, connect two very important cellular mechanisms (SUMOylation and Akt1) to intestinal inflammation and highlight them as potential targets for therapeutic interventions.
SUMOylation pathway alteration coupled with downregulation of SUMO E2 enzyme at mucosal epithelium modulates inflammation in inflammatory bowel disease.Salman Ahmad Mustfa, Mukesh Singh, Aamir Suhail, Gayatree Mohapatra, Smriti Verma, Debangana Chakravorty, Sarika Rana, Ritika Rampal, Atika Dhar, Sudipto Saha, Vineet Ahuja, C. V. Srikanth. Open Biology, June 2017