SUMO proteins in the cardiovascular system: friend or foe?
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REVIEW
SUMO proteins in the cardiovascular system: friend or foe? Prithviraj Manohar Vijaya Shetty1,2, Ashraf Yusuf Rangrez1,3* and Norbert Frey1,3*
Abstract Post-translational modifications (PTMs) are crucial for the adaptation of various signalling pathways to ensure cellular homeostasis and proper adaptation to stress. PTM is a covalent addition of a small chemical functional group such as a phosphate group (phosphorylation), methyl group (methylation), or acetyl group (acetylation); lipids like hydrophobic isoprene polymers (isoprenylation); sugars such as a glycosyl group (glycosylation); or even small peptides such as ubiquitin (ubiquitination), SUMO (SUMOylation), NEDD8 (neddylation), etc. SUMO modification changes the function and/or fate of the protein especially under stress conditions, and the consequences of this conjugation can be appreciated from development to diverse disease processes. The impact of SUMOylation in disease has not been monotonous, rather SUMO is found playing a role on both sides of the coin either facilitating or impeding disease progression. Several recent studies have implicated SUMO proteins as key regulators in various cardiovascular disorders. The focus of this review is thus to summarize the current knowledge on the role of the SUMO family in the pathophysiology of cardiovascular diseases. Keywords: Post-translational modification, SUMO, SUMOylation, Cardiovascular diseases Introduction Every cell has countless biological processes occurring simultaneously, right from its genesis till its terminus, recalibrating its fate perpetually. Each of these processes such as growth, molecule and ion transport or cell division involves molecular pathways with an array of intermediates which ultimately converge on a gene or a group of genes getting modulated, which further regulate a cascade of more such pathways. Although the effect of each pathway is fairly pre-determined, a small molecular modification in one of the players can shift the entire direction of a signaling cascade, altering the fate of the intermediates and definitely changing the outcome. Such modifications, typically post-translational modifications (PTM), can serve as a ‘by-default setting’ in the pathway *Correspondence: [email protected]; [email protected] 1 Department of Internal Medicine III (Cardiology, Angiology, Intensive Care), University Medical Center Kiel, Rosalind‑Franklin Str. 12, 24105 Kiel, Germany Full list of author information is available at the end of the article
or could be brought about by the state at which the cell is at that instant, e.g. in a situation of cellular stress. Small Ubiquitin like Modifier (SUMO) proteins have been recognized as one of the key PTMs modulating the function and half-life of many proteins, thereby serving as master switches in multiple molecular signalling pathways. In the following, we provide a detailed overview on the individual SUMO proteins and their (patho)physiological roles. The SUMO family
SUMO is a conserved family of proteins that h
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