Post-translational modification pathways such as SUMOylation are integral to all cellular processes and tissue homeostasis. We investigated the possible involvement of SUMOylation in the epithelial signalling in Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD). Initially in a murine model of IBD, induced by dextran–sulfate–sodium (DSS mice), we observed inflammation accompanied by a lowering of global SUMOylation of colonic epithelium. The observed SUMOylation alteration was due to a decrease in the sole SUMO E2 enzyme (Ubc9). Mass-spectrometric analysis revealed the existence of a distinct SUMOylome (SUMO-conjugated proteome) in DSS mice with alteration of key cellular regulators, including master kinase Akt1. Knocking-down of Ubc9 in epithelial cells resulted in dramatic activation of inflammatory gene expression, a phenomenon that acted via reduction in Akt1 and its SUMOylated form. Importantly, a strong decrease in Ubc9 and Akt1 was also seen in endoscopic biopsy samples (N = 66) of human CD and UC patients. Furthermore, patients with maximum disease indices were always accompanied by severely lowered Ubc9 or SUMOylated-Akt1. Mucosal tissues with severely compromised Ubc9 function displayed higher levels of pro-inflammatory cytokines and compromised wound-healing markers. Thus, our results reveal an important and previously undescribed role for the SUMOylation pathway involving Ubc9 and Akt1 in modulation of epithelial inflammatory signalling in IBD.

Government of India, Indian Council of Medical Research. There are no conflicts of interest.

A nine-year-old Nepalese girl developed hemiconvulsion, hemiplegia, epilepsy syndrome (HHE syndrome) after an episode of right-sided focal status epilepticus following acute gastroenteritis. She had left middle cerebral artery (MCA) territory infracts due to inherited protein S deficiency.

BackgroundMyc is an essential gene having multiple functions such as in cell growth, differentiation, apoptosis, genomic stability, angiogenesis, and disease biology. A large number of researchers dedicated to Myc biology are generating a substantial amount of data in normal and cancer cells/tissues including Burkitt’s lymphoma and ovarian cancer.ResultsMYCbase (http://bicresources.jcbose.ac.in/ssaha4/mycbase) is a collection of experimentally supported functional sites in Myc that can influence the biological cellular processes. The functional sites were compiled according to their role which includes mutation, methylation pattern, post-translational modifications, protein-protein interactions (PPIs), and DNA interactions. In addition, biochemical properties of Myc are also compiled, which includes metabolism/pathway, protein abundance, and modulators of protein-protein interactions. The OMICS data related to Myc- like gene expression, proteomics expression using mass-spectrometry and miRNAs targeting Myc were also compiled in MYCbase. The mutation and pathway data from the MYCbase were analyzed to look at the patterns and distributions across different diseases. There were few proteins/genes found common in Myc-protein interactions and Myc-DNA binding, and these can play a significant role in transcriptional feedback loops.ConclusionIn this report, we present a comprehensive integration of relevant information regarding Myc in the form of MYCbase. The data compiled in MYCbase provides a reliable data resource for functional sites at the residue level and biochemical properties of Myc in various cancers.

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