Functional decorations: post-translational modifications and heart disease delineated by targeted proteomics

Abstract

The more than 300 currently identified post-translational modifications (PTMs) provides great scope for subtle or dramatic alteration of protein structure and function. Furthermore, the rapid and transient nature of many PTMs allows efficient signal transmission in response to internal and environmental stimuli. PTMs are predominantly added by enzymes, and the enzymes responsible (such as kinases) are thus attractive targets for therapeutic interventions. Modifications can be grouped according to their stability or transience (reversible versus irreversible): irreversible types (such as irreversible redox modifications or protein deamidation) are often associated with aging or tissue injury, whereas transient modifications are associated with signal propagation and regulation. This is particularly important in the setting of heart disease, which comprises a diverse range of acute (such as ischemia/reperfusion), chronic (such as heart failure, dilated cardiomyopathy) and genetic (such as hypertrophic cardiomyopathy) disease states, all of which have been associated with protein PTM. Recently the interplay between diverse PTMs has been suggested to also influence cellular function, with cooperation or competition for sites of modification possible. Here we discuss the utility of proteomics for examining PTMs in the context of the molecular mechanisms of heart disease.

Genome-wide association and pathway analysis of left ventricular function after anthracycline exposure in adults

“…34,35 The observed associations in energetic pathways may suggest that susceptible individuals have less “metabolic reserve” in the face of myocardial injury. Pathway analysis also identified several cellular components and processes previously implicated in myocardial remodeling and response to injury, including glycosylation 36,37 , constituents of the extracellular matrix (ECM) 38 , and proteins involved in ECM-receptor interaction. 39–41 Additionally, two important signaling pathways, wnt and notch, also showed evidence for enrichment.…”

UBC9-Mediated Sumoylation Favorably Impacts Cardiac Function in Compromised Hearts

“…PTM can modulate protein maturation, translocation, protein-protein interactions, half-life and protein function. 44,45 Phosphorylation, 46 glycosylation, 47 ubiquitination 48 and, potentially, NEDDylation 2 can be critical regulators of the protein’s location, function and interactions, allowing a cell to modulate its protein complement in response to the constantly changing demands of the intracellular and extracellular environments. Most PTMs are dynamic in nature and tightly regulated under normal physiological conditions, with the overall PTM profile quickly adapting to changes in the extracellular environment such as nutrient scarcity, physiological stress or deregulation of cellular homeostasis.…”

Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by Electrospray Tandem Mass Spectrometry

“…In this diversity of biomolecules particularly important is an analysis of protein whose dysfunction leads to many of diseases3456. Identification of proteins and the insight into their interactions as well as determination of post-translational modifications contributes to understanding of their biological function or disease state7. Quantitative proteomic analysis has been rapidly growing field that uses mass spectrometry as a leading analytical tool allowing for example to monitor of protein or peptides concentrations89.…”