Ubiquitin-dependent and independent roles of SUMO in proteostasis

Am J Physiol Cell Physiol. 2016 Aug 1;311(2):C284-96. doi: 10.1152/ajpcell.00091.2016. Epub 2016 Jun 22.


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. Owing to a lack of proteostasis, neuronal cells build up toxic protein aggregates in these diseases. Here, we review the role of the ubiquitin-like posttranslational modification SUMO in proteostasis. SUMO alone contributes to protein homeostasis by influencing protein signaling or solubility. However, the main contribution of SUMO to proteostasis is the ability to cooperate with, 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 because of 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.

Keywords: SUMO; SUMO-targeted ubiquitin ligase; neurodegenerative diseases; protein aggregations; proteostasis; ubiquitin.

Publication types

  • Review

MeSH terms

  • Animals
  • Homeostasis / physiology*
  • Humans
  • Neurodegenerative Diseases / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Processing, Post-Translational / physiology
  • SUMO-1 Protein / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism


  • SUMO-1 Protein
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex