Search Results (76)

Oxidative stress disrupts protein function through direct oxidation and triggers adaptive post-translational modifications. Among these, small ubiquitin-like modifier (SUMO)-ylation mediates fast and reversible remodeling of nuclear and cytoplasmic proteins. Redox regulation of the SUMO E1–E2 conjugation complex and specific SUMO proteases, such as SENP1 and SENP3, allows ROS to influence SUMO turnover and substrate selectivity. This defines SUMOylation as a versatile stress-response module under oxidative stress. In this review, we describe oxidative stress-induced remodeling of SUMO conjugation and deconjugation, with a focus on SUMO2/3 responses that transiently adjust transcription, DNA damage repair, and nuclear body dynamics. We discuss disease-relevant SUMO targets and pathological alterations in SUMO regulation across four major disease categories: neurodegenerative diseases, cardiovascular disease, cancer, and diabetes/metabolic diseases. In addition, we summarize emerging evidence connecting redox-sensitive SUMO remodeling to germ-cell function and reproductive health. Together, these perspectives highlight the dual role of SUMOylation as both a driver of stress adaptation and a tractable target for informing therapeutic strategies targeting the SUMO pathway. Full article

Salinity is an abiotic constraint that limits the growth and productivity of tomato (Solanum lycopersicum L.). However, the role of small ubiquitin-like modifier (SUMO) E3 ligases (SIZs) in the salt stress response in tomato remains unknown. Here, a genome-wide analysis identified four SIZ-type genes in tomato, designated SlSIZ1–SlSIZ4. Gene structure and conserved motif analyses revealed the canonical SAP (SAF-A/B, Acinus, and PIAS) domain and the SP-RING (Siz/PIAS RING finger) domain in all SlSIZ proteins. Phylogenetic analysis grouped SIZ proteins from tomato and representative plant species into five major groups (A–E), with SlSIZ members distributed across distinct clades, and members within each clade shared conserved gene structures. Online transcriptome data and our qRT-PCR analyses showed that SlSIZ4 was highly expressed in leaves, flowers, and fruits, whereas SlSIZ1 showed broad expression, with relatively higher levels in roots, flowers, and multiple fruit stages. Under salt stress, abscisic acid (ABA), and methyl jasmonate (MeJA) treatments, the expression of SlSIZ1 and SlSIZ4 was strongly induced, whereas the expression of SlSIZ2 and SlSIZ3 was rarely promoted. In addition, virus-induced gene silencing (VIGS) of SlSIZ1 and SlSIZ4 markedly reduced salt tolerance of tomato seedlings, as reflected by growth inhibition, chlorophyll loss, increased reactive oxygen species (ROS), reduced proline accumulation, and diminished antioxidant gene expressions. Collectively, these findings identify SlSIZ1 and SlSIZ4 as positive regulators of salt stress tolerance in tomato and provide a framework for further dissection of the SlSIZ gene family. Full article

Microgravity during space travel induces significant regulatory changes in the body, posing health risks for astronauts, including alterations in cell morphology and cytoskeletal integrity. The Small Ubiquitin-like Modifier (SUMO) is crucial for cellular adaptation, regulating DNA repair, cytoskeletal dynamics, cell division, and protein turnover—all processes affected by microgravity. To determine the extent to which SUMO mediates the cellular response to microgravity stress, Saccharomyces cerevisiae cells were cultured under normal gravity and simulated microgravity (SMG) in rotating wall vessels. After 12 h of culture, we investigated changes in SUMO modified proteins and protein expression. We identified 347 SUMOylated proteins, 18 of which demonstrated a 50% change in abundance under SMG. Of 3773 proteins identified, protein expression for 34 proteins decreased and 8 increased by over 50% in SMG (p < 0.05). Differentially expressed proteins represented changes in cellular processes for DNA repair, cell division, histone modification, and cytoskeleton regulation. These findings underscore the pivotal role of SUMOylation in orchestrating cellular adaptation to the unique stress of microgravity, revealing potential targets for mitigating spaceflight-induced health risks. Full article

SENP1 (sentrin-specific protease 1) mediates sumoylation, a reversible post-translational modification that attaches the SUMO (small ubiquitin-like modifier) protein to target proteins. These modified proteins are essential in many key cellular processes, including cell cycle regulation, DNA repair, and apoptosis. Disruptions in the balance between sumoylated and desumoylated proteins can lead to various pathological conditions, such as cancer. Experimental data suggest that certain natural compounds, including momordin Ic (Mc), hinokiflavone (HNK), triptolide (TPL), ursolic acid (UA), streptonigrin (SN), vialinin A (VA), thelephantin G (TG), and others, effectively inhibit SENP1 activity, thereby influencing the levels of sumoylated proteins and cellular processes. This article reviews existing knowledge on the structure and function of natural SENP1 inhibitors, particularly their potential application in cancer therapy, including their capacity to overcome resistance to conventional chemotherapies. Some of the natural SENP1 inhibitors tested so far interact directly with the enzyme’s active site. The current understanding of how this interaction occurs is also discussed. Full article

Post-traumatic stress disorder (PTSD) is frequently comorbid with persistent depressive disorder (dysthymia), indicating shared neurobiological pathways that influence stress modulation, emotional regulation, and neurohormonal adaptation. This study examines the roles of serum biomarkers—small ubiquitin-like modifier 1 (SUMO1), malondialdehyde (MDA), fractalkine (CX3CL1), and ubiquitin C-terminal hydrolase L1 (UCHL1)—involved in oxidative stress management, neuroimmune regulation, and neuronal proteostasis. In this cross-sectional analysis, biomarker expression was assessed in 92 male trauma-exposed participants aged 19–50 years, divided into three groups: PTSD duration ≤ 5 years (n = 33, median age 34.0 years [IQR 31.0–41.0]), PTSD duration > 5 years (n = 31, median age 36.0 years [IQR 29.5–41.0]), and controls without current or past PTSD (n = 28, median age 33.5 years [IQR 24.3–41.5]). Participants were stratified into younger (19–34 years) and older (35–50 years) cohorts to account for age-related neurobiological variability. Dysthymic symptomatology was evaluated using the Cornell Dysthymia Rating Scale (CDRS), focusing on chronic subthreshold depressive features. Results indicated a significant association between PTSD and elevated dysthymic symptom burden (p < 0.001), with both PTSD subgroups demonstrating mild to moderate CDRS severity compared to euthymic controls. Biomarker analysis revealed phase-dependent alterations: SUMO1 levels were significantly elevated in the ≤5 years PTSD group compared to controls (p = 0.002), suggesting early compensatory neuroprotection, whereas UCHL1 was markedly increased in the >5 years PTSD group (p = 0.015), which is indicative of chronic neuronal damage and proteostatic disruption. No significant differences were observed in MDA or CX3CL1 across groups (p > 0.05). These findings highlight PTSD’s contribution to sustained affective dysregulation, potentially mediated by temporal shifts in oxidative stress and protein homeostasis markers. Clinically, this supports the utility of biomarker profiling for risk stratification, early intervention, and personalized therapeutic strategies, such as targeted modulation of SUMOylation or UCHL1 activity, to enhance neuroresilience and mitigate progression to severe mood disorders. Full article

The internal mammary arteries (IMAs) and coronary arteries share many common characteristics. The inner layer (tunica intima, or intima) of both arteries is lined with a smooth, longitudinally orientated monolayer of endothelial cells (ECs), connective tissue, and an internal elastic lamina that separates the tunica intima from the tunica media (middle layer). The intima of IMAs is lined with an additional protective layer, the neointima, containing vascular smooth muscle cells (VSMCs). The neointima, located between the intima and internal elastic lamina, protects IMAs from damage by assisting in the remodeling of VSMCs. Coarse longitudinal folds in the internal elastic lamina of IMAs partially prevent the infiltration of VSMCs into damaged IMAs, and intimal thickening is thus less likely to occur. Inflamed IMAs resist the migration of monocytes across the endothelial layer and prevent the formation of lipid-rich macrophages (foam cells) within the subintimal or medial layers of arteries. IMAs are thus less likely to form plaques and develop atherosclerosis (AS). Higher levels of prostacyclin (PGI2) in IMAs prevent blood clotting. The anti-thrombotic agents, and production of tumor necrosis factor α (TNF-α), interferon-γ (INF-γ), and visfatin render IMAs more resistant to inflammation. An increase in the production of nitric oxide (NO) by ECs of IMAs may be due to small ubiquitin-like modifier (SUMO) proteins that alter the nuclear factor kappa B (NF-κB) and TLR pathways. The production of reactive oxygen species (ROS) in IMAs is suppressed due to the inhibition of NADPH oxidase (NOX) by a pigment epithelium-derived factor (PEDF), which is a serine protease inhibitor (SERPIN). In this review, a comparison is drawn between the anatomy of IMAs and coronary arteries, with an emphasis on how ECs of IMAs react to immunological changes, rendering them more suited for coronary artery bypass grafts (CABGs). This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Somatic embryogenesis (SE) is a key plant regeneration technique involving the reprogramming of somatic cells into embryogenic structures. This developmental transition is regulated by complex genetic and epigenetic mechanisms, including post-translational modifications such as SUMOylation—the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target proteins, influencing their function, stability, and interactions. While SUMOylation is known to regulate plant development and stress responses, its role in SE has remained unknown. In this study, we investigated the involvement of the SUMOylation pathway in SE induction in Medicago truncatula. Using BLASTp analysis with known SUMO pathway proteins from Arabidopsis thaliana and Glycine max, we identified 10 homologous genes in M. truncatula. Phylogenetic relationships, gene structure, and conserved motif analyses confirmed their evolutionary conservation and characteristic domains. Expression profiling revealed significant upregulation of SUMO pathway genes—including Mt SUMO2, Mt SAE1-2, Mt SCE1a-b, Mt MMS21, and Mt PIAL2—in embryogenic cell lines during early SE induction. Additionally, in silico prediction of SUMOylation sites and SUMO-interacting motifs (SIMs) in 12 key SE regulatory proteins indicated a broad potential for SUMO-mediated regulation. These findings suggest that SUMOylation may contribute to the acquisition of embryogenic competence during somatic cell reprogramming in plants. Full article

Class IId bacteriocins are linear, unmodified antimicrobial peptides produced by Gram-positive bacteria, and often display potent, narrow-spectrum inhibition spectra. Garvicin Q (GarQ) is a class IId bacteriocin produced by the lactic acid bacterium Lactococcus garvieae. It stands out for its unusual broad-spectrum antimicrobial activity against various bacterial species, including Listeria monocytogenes, Pediococcus pentosaceus, Carnobacterium maltaromaticum, Enterococcus faecalis, and Lactococcus spp. Its protein target is the mannose phosphotransferase system (Man-PTS) of susceptible bacterial strains, though little is known about the precise molecular mechanism behind GarQ’s unusual broad spectrum of activity. In this work, ¹³C- and ¹⁵N-labelled GarQ was recombinantly produced using our previously described “sandwiched” protein expression system in Escherichia coli. We also developed a protocol to purify a uniformly labelled sample of the small ubiquitin-like modifier His₆-SUMO, which is produced as a byproduct of the expression procedure. We demonstrated its use as a “free” protein standard for 3D NMR experiment calibrations. The GarQ solution structure was solved using triple-resonance nuclear magnetic resonance (NMR) spectroscopy and was compared with the structures of other Man-PTS-targeting bacteriocins. GarQ adopts a helix–hinge–helix fold, which is contrary to its structural predictions according to AlphaFold 3. Full article

Introduction: Accumulating evidence indicates that neutrophils undergo reprogramming of their effector functions as they migrate from the bloodstream into an inflamed tissue. Here, we examined the role of the small ubiquitin-like modifier (SUMO) conjugation in modulating neutrophil functional changes in the inflammatory microenvironment. Methods: Primary human and murine neutrophils were used to assess SUMOylation levels in vitro by Western blotting and results were validated in clinical samples from patients undergoing surgery involving hypothermic circulatory arrest. SUMOylation was inhibited with TAK-981, and its impact on neutrophil migration, NETosis, and phagocytosis was assessed in vitro. The in vivo effect of TAK-981 on neutrophil tissue infiltration was further evaluated using a sterile sponge assay in mice. Results: Our results demonstrated that neutrophil SUMOylation was induced by factors of the inflammatory microenvironment (temperature and oxidative stress) and inflammatory stimulants in vitro, and under conditions of general inflammatory activation in patients. Further, we found that blocking SUMOylation with TAK-981 in vitro blunted neutrophil migration and phagocytosis but did not affect NETosis. Notably, TAK-981 treatment reduced neutrophil accumulation in sterile sponges in mice. Conclusions: Our work identifies SUMOylation as a novel mechanism of neutrophil tissue reprogramming. Blocking SUMOylation may provide a therapeutic option to limit the contribution of neutrophils to inflammation-associated tissue damage. Full article

Organophosphorus hydrolase (OPH) is a highly effective bioscavenger for detoxifying hazardous organophosphorus compounds. However, its practical application is hindered by low yield and poor stability. In this study, we employed Small Ubiquitin-like Modifier (SUMO) fusion expression to enhance the solubility of the OPH mutant G5C23-D208G and, for the first time, immobilized the enzyme on a zeolitic imidazolate framework-F (ZIF-F) carrier to improve its stability. The SUMO-G5C23-D208G fusion protein was successfully expressed in Escherichia coli, resulting in a yield that was 2.4 times higher than that of native OPH and an 11-fold increase in solubility. The purified protein achieved a purity of 95%. The immobilized enzyme, SU-MO-G5C23-D208G@ZIF-F, exhibited a farfalle-shaped structure with a diameter of approximately 3–5 μm. Compared to the free enzyme, the immobilized enzyme maintained high catalytic efficiency (kcat/Km = 8.9 × 10⁴ M⁻¹·s⁻¹) and demonstrated enhanced thermal stability, pH stability, and reusability. This study has significantly improved the yield and stability of OPH, thereby supporting its potential for industrial applications. Full article

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at elucidating the role of the small ubiquitin-related modifier (SUMO) in human immunodeficiency virus (HIV) latency in microglial cells. Our findings indicate that SUMOylation may regulate key proteins involved in maintaining viral latency, suggesting a potential mechanism by which HIV evades immune detection in the CNS. By integrating insights from proteomics with functional studies, we anticipate these findings to be the groundwork for future studies on HIV–host interactions and the mechanisms that underlie SUMOylation during latent and productive infection. Full article

The host response to S. Typhimurium infection can be post-transcriptionally regulated by miRNAs. In this study, we investigated the role of miR-215 using both in vivo porcine infection models and in vitro intestinal epithelial cell lines. Several miRNAs were found to be dysregulated in the porcine ileum during infection with wild-type and SPI2-defective mutant strains of S. Typhimurium, with some changes being SPI2-dependent. Notably, miR-215 was significantly downregulated during infection. To explore its functional role, gain-of-function experiments were performed by transfecting porcine intestinal epithelial cells (IPEC-J2) with a miR-215-5p mimic, followed by label-free quantitative (LFQ) proteomic analysis. This analysis identified 157 proteins, of which 35 were downregulated in response to miR-215 overexpression, suggesting they are potential targets of this miRNA. Among these, E2 small ubiquitin-like modifier (SUMO)-conjugating enzyme UBC9 and E3 ubiquitin-ligase HUWE1 were identified as key targets, both of which are upregulated during S. Typhimurium infection. The miR-215-mediated downregulation of these proteins resulted in a significant decrease in overall ubiquitination, a process crucial for regulating inflammasome activation and autophagy. Consistently, inflammasome markers caspase 1 (CASP1) and apoptosis-associated speck-like protein containing a CARD (ASC), as well as autophagy markers microtubule-associated protein 1A/1B-light chain 3 (LC3B) and Ras-related protein Rab-11 (RAB11A), showed decreased expression in miR-215 mimic-transfected and infected IPEC-J2 cells. To further validate these findings, human intestinal epithelial cells (HT29) were used as a complementary model, providing additional insights into conserved immune pathways and extending the observations made in the porcine system. Overall, our findings demonstrate that miR-215 plays a significant role in modulating host inflammasome activation and autophagy by targeting proteins involved in ubiquitination during S. Typhimurium infection. Full article

The promyelocytic leukemia protein (PML) and its associated nuclear bodies have recently emerged as critical regulators of embryonic stem (ES) cell identity. Despite their recognized importance, the complete spectrum of PML-mediated molecular events in ES cells remains unclear. In this report, we study how PML is shaping the proteomic and SUMO proteomic landscape in ES cells. Proteomic profiling of PML-depleted ES cells uncovered a downregulation of self-renewal factors and an upregulation of proteins associated with translation and proteasomal activity, reflecting a cellular transition from pluripotency to differentiation. Importantly, PML promotes the sumoylation of pluripotency-related factors, chromatin organizers, and cell cycle regulators. We identified SALL1 and CDCA8 as novel PML-directed sumoylation targets, both critical for ES cell maintenance. SALL1 sumoylation increases the activation of the Wnt pathway, contributing to its ability to inhibit ES cell differentiation. Similarly, CDCA8 sumoylation enhances its capacity to promote cell proliferation. Collectively, our findings demonstrate that PML regulates ES cell identity by modulating the abundance or sumoylation of key regulators involved in pluripotency and cell cycle progression. Full article

Jararhagin-C (JarC) is a protein from the venom of Bothrops jararaca consisting of disintegrin-like and cysteine-rich domains. JarC shows a modulating effect on angiogenesis and remodeling of extracellular matrix constituents, improving wound healing in a mouse experimental model. JarC is purified from crude venom, and the yield is less than 1%. The aim of this work was to obtain the recombinant form of JarC and to test its biological activity. For this purpose, the bicistronic vector pSUMOUlp1 was used. This vector allowed the expression of the recombinant toxin JarC (rJarC) in fusion with the small ubiquitin-related modifier (SUMO) as well as the SUMO protease Ulp1. After expression, this protease was able to efficiently remove SUMO from rJarC inside the bacteria. rJarC free from SUMO was purified at the expected molecular mass and recognized by polyclonal anti-jararhagin antibodies. In terms of biological activity, both the native and recombinant forms showed no toxicity to the HUVEC cell line CRL1730 and were effective in modulating cell migration activity in the experimental in vitro model. These results demonstrate the successful production of rJarC and the preservation of its biological activity, which may facilitate further investigations into the therapeutic potential of this snake venom-derived protein. Full article

(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms and catalytic cycle, highlighting their significance in regulating key biological functions in thyroid cancer. We discuss the multifaceted roles of SUMOylation in DNA repair mechanisms, protein stability, and the modulation of receptor activities, particularly in the context of thyroid cancer. (3) Results: The aberrant SUMOylation machinery contributes to tumorigenesis through altered gene expression and immune evasion mechanisms. Furthermore, we examine the therapeutic potential of targeting SUMOylation pathways in thyroid cancer treatment, emphasizing the need for further research to develop effective SUMOylation inhibitors. (4) Conclusions: By understanding the intricate roles of SUMOylation in cancer biology, we can pave the way for innovative therapeutic strategies to improve outcomes for patients with advanced tumors. Full article