Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond

J Mol Cell Cardiol. 2014 Jun;71:32-42. doi: 10.1016/j.yjmcc.2013.10.008. Epub 2013 Oct 17.


The ubiquitin-proteasome system (UPS) is the major intracellular degradation system, and its proper function is critical to the health and function of cardiac cells. Alterations in cardiac proteasomes have been linked to several pathological phenotypes, including cardiomyopathies, ischemia-reperfusion injury, heart failure, and hypertrophy. Defects in proteasome-dependent cellular protein homeostasis can be causal for the initiation and progression of certain cardiovascular diseases. Emerging evidence suggests that the UPS can specifically target proteins that govern pathological signaling pathways for degradation, thus altering downstream effectors and disease outcomes. Alterations in UPS-substrate interactions in disease occur, in part, due to direct modifications of 19S, 11S or 20S proteasome subunits. Post-translational modifications (PTMs) are one facet of this proteasomal regulation, with over 400 known phosphorylation sites, over 500 ubiquitination sites and 83 internal lysine acetylation sites, as well as multiple sites for caspase cleavage, glycosylation (such as O-GlcNAc modification), methylation, nitrosylation, oxidation, and SUMOylation. Changes in cardiac proteasome PTMs, which occur in ischemia and cardiomyopathies, are associated with changes in proteasome activity and proteasome assembly; however several features of this regulation remain to be explored. In this review, we focus on how some of the less common PTMs affect proteasome function and alter cellular protein homeostasis. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy".

Keywords: Acetylation; Cardiovascular disease; Methylation; SUMOylation; Ubiquitination; Ubiquitin–proteasome system.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Homeostasis
  • Humans
  • Myocardium / enzymology
  • Myocardium / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Sumoylation*
  • Ubiquitin / metabolism
  • Ubiquitination*


  • Ubiquitin
  • Proteasome Endopeptidase Complex