Coordination of cellular localization-dependent effects of sumoylation in regulating cardiovascular and neurological diseases

Sumoylation, a reversible post-transcriptional modification process, of proteins are involved in cellular differentiation, growth, and even motility by regulating various protein functions. Sumoylation is not limited to cytosolic proteins as recent evidence shows that nuclear proteins, those associated with membranes, and mitochondrial proteins are also sumoylated. Moreover, it is now known that sumoylation plays an important role in the process of major human ailments such as malignant, cardiovascular and neurological diseases. In this chapter, we will highlight and discuss how the localization of SUMO protease and SUMO E3 ligase in different compartments within a cell regulates biological processes that depend on sumoylation. First, we will discuss the key role of sumoylation in the nucleus, which leads to the development of endothelial dysfunction and atherosclerosis. We will then discuss how sumoylation of plasma membrane potassium channel proteins are involved in epilepsy and arrhythmia. Mitochondrial proteins are known to be also sumoylated, and the importance of dynamic-related protein 1 (DRP1) sumoylation on mitochondrial function will be discussed. As we will emphasize through- out this review, sumoylation plays crucial roles in different cellular compartments, which is coordinately regulated by the translocation of various SUMO proteases and SUMO E3 ligase. Comprehensive approach will be necessary to understand the molecular mechanism for efficiently moving around various enzymes that regulate sumoylation within cells.