PROTEIN UBIQUITINOME IN HUMAN SKELETAL MUSCLE INSULIN RESISTANCE

Abstract

Protein ubiquitination is a post-translational modification that is known for its role in regulating the functions and abundance of many proteins through facilitating their degradation by the proteasome. The ubiquitin-proteasome system has been shown to be hyperactivated in the skeletal muscle cells of obese people, which can be linked to insulin resistance. However, no large-scale protein ubiquitination studies at protein as well as site-specific levels in lean insulin sensitive and obese insulin resistant human participants have been reported. In this project we were able to (i) identify and characterize the largest profile of ubiquitination sites in human skeletal muscle cells from lean-insulin sensitive people; (ii) identify the differential regulation in total protein ubiquitination, abundance of key insulin signaling pathway subunits, and site-specific protein ubiquitination between lean-insulin sensitive and obese-insulin resistant people and investigated the impact of proteasome inhibition and insulin stimulation on them. This project provides new knowledge and presents new targets that can be further studied to understand the pathological development of insulin resistance.