Abstract
Conjugation with the small ubiquitin-like modifier (SUMO) constitutes a key post-translational modification regulating the stability, activity, and subcellular localization of its target proteins. However, the vast numbers of identified SUMO substrates obscure a clear view on the function of SUMOylation in health and disease. This article presents a comprehensive review on the physiological relevance of SUMOylation by discussing how global SUMOylation levels—rather than specific protein SUMOylation—shapes the immune response. In particular, we highlight the growing body of work on SUMOylation in intestinal pathologies, because of the unique metabolic, infectious, and inflammatory challenges of this organ. Recent studies show that global SUMOylation can help restrain detrimental inflammation while maintaining immune defenses and tissue integrity. These results warrant further efforts to develop new therapeutic tools and strategies to control SUMOylation in infectious and inflammatory disorders.
Highlights
Post-translational modifications (PTMs) form a crucial layer of regulation that substantially increases the functional repertoire of the existing proteome
A comprehensive analysis of 22 small ubiquitin-like modifier (SUMO) proteomic studies using human cells identified more than 3,000 SUMO targets with a large portion of these being transcriptional factors and chromatin-associated proteins, linked to accessing genetic information [9]
For the SUMO2/3 isoforms, this increase is readily appreciated by the detection of a high-molecular “smear”— a broad signal representing the large variety of SUMOylated proteins of different sizes—in Western blots
Summary
Post-translational modifications (PTMs) form a crucial layer of regulation that substantially increases the functional repertoire of the existing proteome. One critical example is small ubiquitin-like modifier (SUMO) modification (SUMOylation), in which SUMO is covalently, but reversibly, linked to the lysine residues of target proteins. Because SUMOylation is highly responsive to endogenous and environmental stressors and because a large number of SUMO targets are transcription factors or nuclear proteins, this PTM is increasingly recognized as a key regulator in health and disease [1,2,3]. What is striking is that, following cell stress, SUMOylation rapidly increases across a broad set of target proteins and effectively re-programs cellular responses. This review summarizes the emerging knowledge of how this global SUMOylation response helps maintain cellular and tissue integrity by preventing exaggerated inflammation
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