Coordination of Cellular Localization-Dependent Effects of Sumoylation in Regulating Cardiovascular and Neurological Diseases

Abstract

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 throughout 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.

Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases

“…Different posttranslational modifications provide different physiological functions to Drp1, and next, we will give a detailed review of the Drp1 posttranslational modifications in the pathogenesis of the neural system dysfunctions and neurodegenerative diseases. It is noteworthy that overexpression of Drp1 cannot cause the fragmentation of mitochondria, as the activation of Drp1 activity is determined by the transport of Drp1 from cytoplasm to mitochondria caused by various ( Figure 2) posttranslational modifications (Abe et al, 2017;Choi et al, 2017;C. Guo et al, 2013;Haun et al, 2013;Park, Ko, Hwang, & Koh, 2015;Rizza et al, 2018; H. Wang et al, 2011;Yang et al, 2017).…”

Synaptic localization of the SUMOylation‐regulating protease SENP5 in the adult mouse brain

“…The post‐translational modification of proteins through the addition of small ubiquitin‐like modifier (SUMO) proteins regulates a broad range of cellular functions including mitosis, cell differentiation, and synaptic transmission (Deyrieux & Wilson, ; Gwizdek, Casse, & Martin, ; Henley, Craig, & Wilkinson, ; Mukhopadhyay & Dasso, ). SUMOs have thus been implicated in several disease states such as cancer, diabetes, cardiovascular disease, and neurological disorders (Abe et al, ; Eifler & Vertegaal, ; Henley et al, ; Lee, Choi, & Baek, ; Zhang, Chen, Zhou, Yang, & Wang, ). SUMOs are covalently attached to target proteins by conjugating enzymes in a process called SUMOylation.…”

Knockdown of AMPKα2 impairs epithelial‑mesenchymal transition in rat renal tubular epithelial cells by downregulating ETS1 and RPS6KA1

“…The c-terminal domain can be activated by erK1/2 phosphorylation and calcium-dependent kinase (33). activated rPS6Ka1 phosphorylates creB, nF-κB and other transcription factors (34). rPS6Ka1 cause apoptosis of renal tubular epithelial cells during renal fibrosis (35), although to the best of our knowledge, eMT of renal tubular epithelial cells has not yet been reported.…”