Cellular proteomes are continuously undergoing alterations as a result of new production of proteins, protein folding and degradation of proteins. The proper equilibrium of these processes is known as proteostasis, implying that proteomes are in homeostasis. Stress conditions can affect proteostasis due to the accumulation of misfolded proteins as a result of overloading the degradation machinery. Proteostasis is affected in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and multiple polyglutamine disorders including Huntington's disease. Due to a lack of proteostasis, neuronal cells build up toxic protein aggregates in these diseases. Here, we review the role of the ubiquitin-like post-translational modification SUMO in proteostasis. SUMO alone contributes to protein homeostasis by influencing protein signalling or solubility. However, the main contribution of SUMO is the ability to cooperate, complement and balance the ubiquitin-proteasome system at multiple levels. We discuss the identification of enzymes involved in the interplay between SUMO and ubiquitin, exploring the complexity of this crosstalk which regulates proteostasis. These enzymes include SUMO-targeted ubiquitin ligases and ubiquitin proteases counteracting these ligases. Additionally, we review the role of SUMO in brain related diseases, where SUMO is primarily investigated due to its role during formation of aggregates, either independently or in cooperation with ubiquitin. Detailed understanding of the role of SUMO in these diseases could lead to novel treatment options.
- neurodegenerative diseases
- protein aggregations
- Copyright © 2016, American Journal of Physiology - Cell Physiology