Degradative proteomics and disease mechanisms

Abstract

Protein degradation is a fundamental biological process, which is essential for the maintenance and regulation of normal cellular function. In humans and animals, proteins can be degraded by a number of mechanisms: the ubiquitin-proteasome system, autophagy and intracellular proteases. The advances in contemporary protein analysis means that proteomics is increasingly being used to explore these key pathways and as a means of monitoring protein degradation. The dysfunction of protein degradative pathways has been associated with the development of a number of important diseases including cancer, muscle wasting disorders and neurodegenerative diseases. This review will focus on the role of proteomics to study cellular degradative processes and how these strategies are being applied to understand the molecular basis of diseases arising from disturbances in protein degradation.

Uncovering Ubiquitin and Ubiquitin-like Signaling Networks

“…(283) Systematic, unbiased, and proteome-wide studies on protein ubiquitylation and UBL conjugation will strongly improve our understanding of these modifications in the near future, particularly with respect to the identification of target proteins for the vast numbers of ligases and proteases in the system and to identify the targets that are dynamically regulated in response to a wide variety of stimuli. This is furthermore relevant for the detailed understanding of deregulation of ubiquitin signaling in human diseases 108,209−211,284 and for the development of drugs that target components of ubiquitin signaling cascades. 285,286 …”