Mini-reviewSUMOylation homeostasis in tumorigenesis
Introduction
Small ubiquitin-like modifier (SUMO) is used to modify a variety of proteins by its covalent attachment to these proteins as a posttranslational modification (PTM). This highly dynamic and reversible modification is an important stress response mechanism in cells and appears to be dysregulated in many cancers. There are 5 mammalian SUMO isoforms: SUMO1, SUMO2/3, SUMO4 and SUMO5. Although the SUMO isoform nomenclature is inconsistent, the human SUMO2 and SUMO3 proteins share 97% sequence identity and cannot be distinguished by antibodies; however, SUMO1 is quite different from SUMO2/3, as 53% of the sequence of SUMO1 differs from that of SUMO2/3 [33]. SUMO1 and SUMO2/3 conjugate distinct substrates in vivo and show different abilities to form SUMO chains. The difference in chain forming ability is attributed to the Lys residues near the amino termini of SUMO2/3, which serve as SUMO acceptor sites, while in SUMO1, these residues are not readily apparent. SUMO1 and SUMO2/3 paralogues are characterized by proteolytic maturation, which refers to exposing a carboxy-terminal diglycine (GG) motif by the sentrin specific peptidase (SENP). SUMO4, another SUMO family member, is similar to SUMO2/3 except that the SUMO4 sequence contains a proline (Pro 90) instead of a glutamine that leads to inert maturation by SENP. SUMO5, a newly discovered SUMO variant, was recently found in several primate tissues [56]. Despite the differences among these isoforms, the enzymes that activate and conjugate each type of SUMO protein are the same.
Section snippets
The process of SUMOylation and deSUMOylation
The attachment of SUMO is catalyzed through an enzymatic cascade involving an E1 activating enzyme, an E2 conjugating enzyme and an E3 ligase [16] (Fig. 1). The SUMO E1 enzyme, a heterodimer composed of SUMO-activating enzyme subunit 1 (SAE1) and SAE2, forms the C-terminus of SUMO [11]. Once the SUMO adenylate is formed, it is transferred to UBC9, the single E2 conjugating enzyme, forming an E2-SUMO thioester bond via an isopeptide linkage to a target lysine residue. Although very few proteins
The physiological function of SUMOylation
Recent data suggest that up to 3000 human proteins are modified by SUMO under certain circumstances [39]. SUMO is mainly found in the nucleus and is essential for the regulation of various nuclear processes such as gene expression, genome maintenance and DNA damage repair and, therefore, cell cycle control and nucleocytoplasmic transport. In addition to its impact on gene networks, SUMOylation plays direct roles in transcriptional regulation and affects protein stability, activity and
Aberrant SUMO modification contributes to various tumors
Given the essential role of SUMOylation in regulating various biological processes, it is not surprising that SUMOylation plays a crucial role in tumorigenesis. To date, numerous aberrantly SUMOylated proteins have been identified in multiple cancers (Fig. 3 and Table 2). However, these findings on the mechanistic link between SUMOylation and tumorigenesis represent merely the tip of the iceberg.
Conclusion and future perspectives
In recent years, we have seen a renaissance of interest in the field of posttranslational modification. An extensive array of ubiquitylation and phosphorylation events have been uncovered. However, there remains a limited understanding of SUMOylation events. Fortunately, with the rapid development of bioinformatics and mass spectrometry, a variety of methods can be used to explore SUMO-modified substrates and sites accurately and efficiently. These advancements have aided in deciphering the
Declaration of competing interest
The authors declare that they have no competing interests.
Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (No.81672709 to J.H.) and the Science and Technology Commission of Shanghai (17DZ2260100 to X.F.).
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SUMOylation of SYNJ2BP-COX16 promotes breast cancer progression through DRP1-mediated mitochondrial fission
2022, Cancer LettersCitation Excerpt :Sentrin/small ubiquitin-like modifier (SUMO) proteins share structural similarities with ubiquitin, and their conjugation to substrates occurs through a related enzymatic cascade involving the sequential action of an E1 activating enzyme, an E2 conjugating enzyme and an E3 ligase enzyme. SUMOylation affects the development of cancer through multiple signaling pathways that regulate protein stability [6,7], protein localization [8,9], transcription [10] and DNA damage repair [11], which ultimately provide links to cell differentiation, senescence, apoptosis and the epithelial-mesenchymal transition (EMT) [12]. Here, we aimed to identify and verify a new SUMOylation fusion protein, Synaptojanin 2 binding protein-Cytochrome-c oxidase 16 (SYNJ2BP‐COX16), in tumors.
A proximity ligation assay (PLA) based sensing platform for the ultrasensitive detection of P53 protein-specific SUMOylation
2022, Process BiochemistryCitation Excerpt :SUMOylation is important for regulating cellular processes through interfering major oncogenes pathways, such as interfere c-Myc gene expression to targeting the anticancer therapy when these oncogenes are activated by SUMOylation [5–10]. So, SUMOylation is a potential target for developing cancer therapies and other life-threatening diseases [11–15]. In addition, SUMOylation regulates the DNA-damage-related human diseases, such as pathogen infection and heart diseases.
Post-translational modification of RAS proteins
2021, Current Opinion in Structural BiologyCitation Excerpt :While this small ubiquitin-like modifier (SUMO) is similar in size to ubiquitin, SUMOylation does not appear to initiate degradation. Rather, one well-known role of SUMOylation lies in the regulation of cell growth, migration, and tumorigenesis [118]. SUMOylation of RAS proteins occurs at a conserved lysine, Lys42, which is proximal to the effector region (residues 30–40).
Ginkgoic acid impedes gastric cancer cell proliferation, migration and EMT through inhibiting the SUMOylation of IGF-1R
2021, Chemico-Biological InteractionsCitation Excerpt :Sumoylation and desumoylation are involved in a variety of cellular processes such as nuclear-to-cytosolic translocation, transcriptional regulation, apoptosis, protein stability, response to stress, and stem cell/progenitor maintenance, pluripotency, and differentiation [29]. In particular, the dysregulation of SUMOylation or deSUMOylation processes is implicated in the development of cancers [30]. The inhibition of protein SUMOylation both in vitro and in vivo by GA is explained by its direct binding to E1, which prevents the formation of the E1-SUMO intermediate [17].