ROLE OF UBIQUITIN E3 LIGASE, ANGIOGENIC AND APOPTOTIC SIGNALING IN DIABETES

Abstract

Diabetes is a metabolic disorder prevalent all over the globe. It is becoming more concerned disease as it is paving the way to other chronic diseases such as heart disease, stroke, and vision loss and kidney failure. Protein quality control system depends on molecular chaperones and ubiquitin E3 ligase for maintaining the balance between folded and degraded proteins. HIF1α, a key angiogenesis marker is regulated by Stub1 and Hsp40/70 under high glucose conditions and thus, affects the insulin pathway. In this study, we aimed at studying the role of ubiquitin E3 ligase, apoptosis and angiogenesis in Type II diabetes. This study involved the identification of major ubiquitin E3 ligases, development of protein-protein interaction network among ubiquitin E3 ligases, apoptotic and angiogenesis markers and finally, the drug designing. We identified Stub1 as a key molecule that interacts and controls the activity of other signaling proteins such as NOS1, HIF1α, FOXO1, FOXO3, SGK1, Akt1 and others. This finding suggests that if Stub1 is therapeutically targeted then it might prevent the diabetic complication. Virtual screening of commercially available natural compound products of ZINC Database and molecular docking studies provided ethyl 5-[(diphenylcarbamoyl) oxy]-2-(4-methoxyphenyl)-1-benzofuran-3-carboxylate as a potent inhibitor against Stub1. For virtual screening, Argus Lab 4.0 software and for molecular docking studies, Argus lab 4.0 and Virtual Molegro docker were used. Thus, ethyl 5-[(diphenylcarbamoyl) oxy]-2-(4-methoxyphenyl)-1-benzofuran-3-carboxylate might be a potent drug molecule against Stub1 and could provide better cure for Type 2 diabetes.