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Neuromol Med (2013) 15:639660 DOI 10.1007/s12017-013-8258-6
REVIEW PAPER
SUMO Rules: Regulatory Concepts and Their Implication in Neurologic Functions
Mathias Droescher Viduth K. Chaugule
Andrea Pichler
Received: 27 June 2013 / Accepted: 8 August 2013 / Published online: 30 August 2013 Springer Science+Business Media New York 2013
Abstract Posttranslational modication of proteins by the small ubiquitin-like modier (SUMO) is a potent regulator of various cellular events. Hundreds of substrates have been identied, many of them involved in vital processes like transcriptional regulation, signal transduction, protein degradation, cell cycle regulation, DNA repair, chromatin organization, and nuclear transport. In recent years, protein sumoylation increasingly attracted attention, as it could be linked to heart failure, cancer, and neuro-degeneration. However, underlying mechanisms involving how modication by SUMO contributes to disease development are still scarce thus necessitating further research. This review aims to critically discuss currently available concepts of the SUMO pathway, thereby highlighting regulation in the healthy versus diseased organism, focusing on neurologic aspects. Better understanding of differential regulation in health and disease may nally allow to uncover pathogenic mechanisms and contribute to the development of disease-specic therapies.
Keywords SUMO E1 activating enzyme E2
conjugating enzyme E3 ligases SUMO-specic
proteases SIM SUMO consensus SUMO paralogs
Deregulation Neurological disorders
Introduction
Posttranslational modications are efcient tools within a cellular system to quickly and reversibly modulate protein functions without the need of de novo protein synthesis. Such a ne-tuning mechanism usually results in regulating the choice of inter- and intra-molecular binding surfaces that can have diverse consequences, like on protein stability, conformation, activity, and intracellular localization to adapt a target protein to the changing needs of a cell. Small chemical modiers, such as phosphorylation, acetylation, and methylation, are well established as cellular regulators, as they are heavily investigated since a long time. Modication by ubiquitin or the small ubiquitin-like modier (SUMO) stands apart in that the modier itself is a small polypeptide. Ubiquitination is best known for its role in protein degradation (reviewed in Pickart 2001), but has also several nonproteolytic regulatory functions (reviewed in Komander and Rape 2012). SUMO is structurally related to ubiquitin and is also conjugated to target lysines via a hierarchical enzymatic cascade (Bayer et al. 1998; Kim et al. 2002; Pickart 2001). In the past two decades, hundreds...