Mechanisms, regulation and consequences of protein SUMOylation

Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
Biochemical Journal (Impact Factor: 4.4). 06/2010; 428(2):133-45. DOI: 10.1042/BJ20100158
Source: PubMed

ABSTRACT The post-translational modification SUMOylation is a major regulator of protein function that plays an important role in a wide range of cellular processes. SUMOylation involves the covalent attachment of a member of the SUMO (small ubiquitin-like modifier) family of proteins to lysine residues in specific target proteins via an enzymatic cascade analogous to, but distinct from, the ubiquitination pathway. There are four SUMO paralogues and an increasing number of proteins are being identified as SUMO substrates. However, in many cases little is known about how SUMOylation of these targets is regulated. Compared with the ubiquitination pathway, relatively few components of the conjugation machinery have been described and the processes that specify individual SUMO paralogue conjugation to defined substrate proteins are an active area of research. In the present review, we briefly describe the SUMOylation pathway and present an overview of the recent findings that are beginning to identify some of the mechanisms that regulate protein SUMOylation.

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    • ", 2012 ) . However , insights into its fundamental role in regulating metabolism are still in the nascent stages ( Wilkinson and Henley , 2010 ) . Our study elaborates on how SUMOylation influences this cellular process and defines the SUMOylation changes that occur to maintain homeostasis in conditions of metabolic stress . "
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    ABSTRACT: SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell's energy equilibrium. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 07/2015; 12(5). DOI:10.1016/j.celrep.2015.07.002 · 8.36 Impact Factor
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    • "SUMO deconjugation is performed by a family of cysteine proteases, generically named as SENPs. Six SENP members were first described (Wilkinson and Henley, 2010) and very recently three new members, DESI1, DESI2 and USPL1, have been added to the group of SUMO deconjugating enzymes (Schulz et al., 2012; Shin et al., 2012). The attachment of SUMO moieties to their substrate targets regulates many relevant physiological processes by modulating enzyme activity, activating transcription factors (TFs), shifting protein subcellular localizations, and eventually, determining their substrate fate. "
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    ABSTRACT: Sumoylation is a reversible post-translational modification that regulates different cellular processes by conjugation/deconjugation of SUMO moieties to target proteins. Most work on the functional relevance of SUMO has focused on cell cycle, DNA repair and cancer in cultured cells, but data on the inter-dependence of separate components of the SUMO pathway in highly specialized tissues, such as the retina, is still scanty. Nonetheless, several retinal transcription factors (TFs) relevant for cone and rod fate, as well as some circadian rhythm regulators, are regulated by sumoylation. Here we present a comprehensive survey of SUMO pathway gene expression in the murine retina by quantitative RT-PCR and in situ hybridization (ISH). The mRNA expression levels were quantified in retinas obtained under four different light/dark conditions, revealing distinct levels of gene expression. In addition, a SUMO pathway retinal gene atlas based on the mRNA expression pattern was drawn. Although most genes are ubiquitously expressed, some patterns could be defined in a first step to determine its biological significance and interdependence. The wide expression of the SUMO pathway genes, the transcriptional response under several light/dark conditions, and the diversity of expression patterns in different cell layers clearly support sumoylation as a relevant post-translational modification in the retina. This expression atlas intends to be a reference framework for retinal researchers and to depict a more comprehensive view of the SUMO-regulated processes in the retina. © 2015. Published by The Company of Biologists Ltd.
    Biology Open 01/2015; 4(2). DOI:10.1242/bio.201410645 · 2.42 Impact Factor
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    • "Sumoylation, a post-translational protein modification, involves the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target proteins. Although SUMO is typically conjugated to a specific lysine (Lys) residue within the consensus motif ψKxE/D (where ψ is an aliphatic amino acid) in the target protein, sumoylation can occur at Lys residues outside of the consensus, and not all the consensus Lys residues are sumoylated [7]. The mechanism of the conjugation of SUMO to its target protein is similar to that of ubiquitination. "
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    ABSTRACT: Mutations in superoxide dismutase 1 (SOD1) are a major cause of familial amyotrophic lateral sclerosis (ALS), whereby the mutant proteins misfold and aggregate to form intracellular inclusions. We report that both small ubiquitin-like modifier (SUMO) 1 and SUMO2/3 modify ALS-linked SOD1 mutant proteins at lysine 75 in a motoneuronal cell line, the cell type affected in ALS. In these cells, SUMO1 modification occurred on both lysine 75 and lysine 9 of SOD1, and modification of ALS-linked SOD1 mutant proteins by SUMO3, rather than by SUMO1, significantly increased the stability of the proteins and accelerated intracellular aggregate formation. These findings suggest the contribution of sumoylation, particularly by SUMO3, to the protein aggregation process underlying the pathogenesis of ALS.
    PLoS ONE 06/2014; 9(6):e101080. DOI:10.1371/journal.pone.0101080 · 3.23 Impact Factor
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