Identification and evaluation of scaffold protein mediated type 2 diabetes mechanisms

Abstract

Since scaffold proteins are identified as key regulatory modulators of cellular functions, several studies have been tried to discover specific scaffolding functions and predict novel scaffold proteins. Although scaffold proteins are thought to play important roles in disease development and treatments, comprehensive researches for understanding of disease-associated scaffold protein are lacking. In this study, we have developed the methods to prioritize diabetes-associated scaffold proteins and identify novel scaffold protein-mediated type 2 diabetes (T2D) mechanisms. We predicted novel scaffold proteins and integrated the known and predicted scaffold proteins with their partner proteins based on different criteria. We collected various resources related to type 2 diabetes and comprehensively analyzed pathways to understand the mechanisms of T2D. Diabetes-associated scaffold proteins are defined by direct and indirect association with known diabetes-related genes and their functions. With support evidences we selected the diabetes-associated functional scaffold protein modules and finally suggested the scaffold protein-mediated diabetes mechanism models. We also implemented the web-based system for browsing, searching and analyzing of diabetes-associated scaffold protein modules to study novel mechanisms or discover novel therapeutic target candidates. This versatile platform can be directly used for identification and prioritization of novel therapeutic targets and regulatory mechanisms for type 2 diabetes.