Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond - PubMed (original) (raw)

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Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond

Ziyou Cui et al. J Mol Cell Cardiol. 2014 Jun.

Abstract

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.

© 2013.

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Figures

Figure 1

Figure 1

Schematic diagram of the effects of PTMs on proteasome function and their involvement in cardiovascular diseases. The 19S proteasome is shown in purple while the α and β rings of the 20S proteasome are shown in blue and red, respectively. Several cardiovascular diseases are known to alter proteasome PTMs including atherosclerosis, diabetes, hypertension, ischemia/reperfusion and heart failure. Atherosclerosis, diabetes and hypertension, all cause increases in reactive nitrogen species (RNS), resulting in nitration of proteasome subunits, which results in improved proteasome assembly and function. Ischemic injury causes oxidative stress leading to carbonylation of proteasome subunits and impaired proteasome activity. Decreased α7 phosphorylation at residue S250, decreased ATPase activity, and impaired docking of the 19S to the 20S was detected in human end stage heart failure when compared to control hearts [88]. ROS, reactive oxygen species. HNE, hydroxy-nonenalyation.

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References

    1. Goll DE, Neti G, Mares SW, Thompson VF. Myofibrillar protein turnover: the proteasome and the calpains. Journal of animal science. 2008;86:E19–35. - PubMed
    1. Schubert U, Anton LC, Gibbs J, Norbury CC, Yewdell JW, Bennink JR. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature. 2000;404:770–4. - PubMed
    1. Xu G, Paige JS, Jaffrey SR. Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nature biotechnology. 2010;28:868–73. - PMC - PubMed
    1. Peters JM. Proteasomes: protein degradation machines of the cell. Trends in biochemical sciences. 1994;19:377–82. - PubMed
    1. Brooks P, Fuertes G, Murray RZ, Bose S, Knecht E, Rechsteiner MC, et al. Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. The Biochemical journal. 2000;346:155–61. Pt 1. - PMC - PubMed

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