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The role of mesenchymal stem cells in attenuating inflammatory bowel disease through ubiquitination.

Inflammatory bowel disease (IBD), a condition of the digestive tract and one of the autoimmune diseases, is becoming a disease of significant global public health concern and substantial clinical burden. Various signaling pathways have been documented to modulate IBD, but the exact activation and regulatory mechanisms have not been fully clarified; thus, a need for constant exploration of the molecules and pathways that play key roles in the development of IBD. In recent years, several protein post-translational modification pathways, such as ubiquitination, phosphorylation, methylation, acety

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… Yang W et al. experimentally demonstrated that increased SUMOylating has a neuroprotective effect and seems necessary for survival, at least under certain conditions (ischemia) ( 83 ). … Sumoylation: a regulatory protein modification in health and disease. Annu Rev Biochem. (2013) 82:357–85. doi: 10.1146/annurev-biochem-061909-093311 84. Yang W, Sheng H, Warner DS, Paschen W. Transient global cerebral ischemia induces a massive increase in protein sumoylation. …

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and b

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… A study focusing on the conjugation machinery for SUMOylation in response to low dose (100 μM) ascorbate performed SUMO-1 IP followed by ESI-FT ICR MS in neuroblastoma cell line SH-SY5Y [ 162 ]. … This study identified, among others, DTD2 and MGAT5B, two proteins without predicted SUMOylation site, related to translation and glycosylation, respectively, with increased abundance following ascorbate (but not hydrogen peroxide) treatment. …

Student Summer Research Awards - SSRAAbstracts of the SSRA September 2022 meeting, UCD School of Medicine.

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NF-κB: master regulator of cellular responses in health and disease.

The NF-κB transcription control proteins play widespread roles in cellular behavior, regulating immune responses, inflammation, cell survival, proliferation, and development. Here, we attempt to comprehensively review these diverse functions and underlying mechanisms, leading readers to relevant references of both historic and topical importance. Because of the huge number of NF-κB control mechanisms and functions, and the vast literature that describes these, being comprehensive is a daunting task but we hope that readers will find clues to lead them to whatever understanding they may seek. A

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… SUMOylation is a less well-studied PTM of NF-κB but has been shown to play a role in its regulation. SUMOylation of RelA can lead to its nuclear export and transcriptional repression, while SUMOylation of IκBα can stabilize it and prevent its degradation [ 104 ]. … SUMOylation of other NF-κB subunits, such as p50 and RelB, can also influence their activity and function [ 117 ]. These PTMs provide an additional layer of regulation, allowing cells to rapidly adjust NF-κB activity in response to changing environmental conditions. …

Убиквитационное регулирование гликолитического фермента MCT4 в поощрении астроцитной реактивности во время нейроинфламмации.

Одним из гистопатологических признаков нервно-воспалительных заболеваний, таких, как множественный склероз (MS), является появление астроцитной реактивности. Накопление данных свидетельствует о том, что чрезмерный гликолиз может привести к астроцитной реактивности и способствовать нейроэнфламативным реакциям. Однако сложные механизмы, лежащие в основе метаболического перепрограммирования астроцитов в направлении гликолиза, остаются в значительной степени неизвестными. Здесь мы провели эксперименты in vitro с использованием первичных астроцитов и в vivo в экспериментальной аутоиммунной энцефало

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… Post-translational modifications (PTMs), including ubiquitination, SUMOylation and acetylation, play a pivotal role in regulating protein stability, subcellular localization and protein-protein interaction. … SUMOylation by FBW7 and β-TRCP led to increased protein stability of MCT4 [ 40 ]. E3 ubiquitin ligase SYVN1-mediated ubiquitination regulated MCT4 subcellular distribution, thereby enhancing its membrane localization for glycolysis-related functions [ 34 ]. …

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN

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… These include ADP-ribosylation, ubiquitination, sumoylation, methylation, acetylation, and phosphorylation. … Histone Modifications: Now Summoning Sumoylation. Proc. Natl. Acad. Sci. 100, 13118–13120. 10.1073/pnas.2436173100 Nigris F., Ruosi C., Napoli C. (2021). Clinical Efficiency of Epigenetic Drugs Therapy in Bone Malignancies. Bone 143 (February), 115605. 10.1016/j.bone.2020.115605 O’Connor O. …

The therapeutic potential of colchicine in oncology studies: from structural modification and targeted delivery to clinical management.

Colchicine, a classical microtubule-targeting agent (MTA), exhibits remarkable anti-tumor potential, but its clinical translation is severely restricted by a narrow therapeutic window, systemic off-target toxicity, and complex pharmacokinetic vulnerabilities. Driven by the objective of "toxicity reduction and efficacy enhancement," this review comprehensively summarizes colchicine's multidimensional translational research. First, precise chemical modifications of its tricyclic scaffold and multi-site synergistic strategies are analyzed, exploring structure-activity relationship (SAR) mechanism

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… For instance, in multiple myeloma, combining colchicine with bortezomib inhibits SAE1-mediated SUMOylation and p27 nuclear export, effectively restoring cell cycle arrest via mechanistically coupled synergy ( Wang et al., 2025 ). … SAE1 promotes tumor cell malignancy via SUMOylation and liquid-liquid phase separation facilitated nuclear export of p27. Acta Pharm. Sin. B 15, 1991–2007. 10.1016/j.apsb.2025.02.011 Wilhelm S., Tavares A. J., Dai Q., Ohta S., Audet J., Dvorak H. F., et al. (2016). …

Метаболомическое исследование синдромов миэлодипластика, множественной миеломы и гомозиговой β-Талассемии.

Хроническая анемия, как правило, диагностируется у пожилых людей и служит важным показателем как реактивных, так и клональных заболеваний. Многие основные заболевания, такие, как миэллодипластические синдромы и множественная миелома, более распространены среди пожилых людей, в то время как новые терапевтические подходы превратили педиатрические расстройства слабого прогноза, такие, как бета-талассемия, в хроническое заболевание пожилых людей. Таким образом, растущая распространенность хронической анемии в пожилом возрасте в значительной степени объясняется более частыми диагностическими и тера

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… Among PK isoforms, PKM2 is predominant in tumor cells and is associated with the proliferative and differentiative capacity of myeloid cells, enhancing the development of hematopoietic malignancies via SUMOylation processes [ 18 , 82 ]. … SUMOylation Disassembles the Tetrameric Pyruvate Kinase M2 to Block Myeloid Differentiation of Leukemia Cells. Cell Death Dis. 2021;12:101. doi: 10.1038/s41419-021-03400-9. 83. Wang L., Yang L., Yang Z., Tang Y., Tao Y., Zhan Q., Lei L., Jing Y., Jiang X., Jin H., et al. …

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and

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… Importantly, the transcriptional activity of nSREBP-2 is also modulated by various post-translational modifications, including phosphorylation, acetylation, and sumoylation. … Additionally, nSREBP-2 at Lys464 is also modified by sumoylation to decrease transcriptional activity ( 54 ). …

The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic framework

NF2-Related Schwannomatosis (NF2): Molecular Insights and Therapeutic Avenues.

NF2-related schwannomatosis (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth.

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… Interestingly, it has been found that the Sumoylation of Merlin is essential for its tumor-suppressive activity. … Merlin sumoylation is required for its tumor suppressor activity Oncogene 2014 33 4893 4903 10.1038/onc.2013.438 24166499 40. Jin H. Sperka T. Herrlich P. Morrison H. …

PPARs in Irradiation-Induced Gastrointestinal Toxicity.

The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. Although the benefits of this treatment are well established, many patients experience distressing complications due to injury to normal tissue. These side effects are related to inflammatory processes, and they decrease therapeutic benefit by increasing the overall treatment time. Emerging evidence indicates that PPARs and their ligands are important in the modulation of immune and inflammatory reactions. This paper discusses the effects of abdominal irradiation on PPARs, their role and functions in i

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… Ligand-binding of PPAR- γ induces the SUMOylation of a fraction of some PPAR- γ molecules, which bind to NCoR and prevent its clearance from the promoter. This leads to a sustained repressed state. … A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ . Nature. 2005;437(7059):759–763. doi: 10.1038/nature03988. 14. Bailey ST, Ghosh S. PPAR'ting ways with inflammation. Nature Immunology. 2005;6(10):966–967. doi: 10.1038/ni1005-966. 15. …

Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.

Histone methyltransferases (HMTs) and histone demethylases (HDMs) are critical enzymes that regulate chromatin dynamics and gene expression through the addition and removal of methyl groups on histone proteins. HMTs, such as PRC2 and SETD2, are involved in the trimethylation of histone H3 at lysine 27 and lysine 36, influencing gene silencing and activation. Dysregulation of these enzymes often leads to abnormal gene expression and contributes to tumorigenesis. In contrast, HDMs including KDM7A and KDM2A reverse these methylation marks, and their dysfunction can drive disease progression. In c

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… Repression of PRDM16’s transcriptional activity due to sumoylation could impact AD pathogenesis as sumoylation plays a role in AD [ 44 ]. …

The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing.

p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the 'guardian of the genome' and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni syndrome (LFS), the inherited cance

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… p73 2.1. p53 p53 is a protein of the domain structure and a transcription factor binding specifically to DNA consensus sequence consisting of two consecutive half-sites as a tetramer [ 8 ]. p53 is known to undergo multiple post-translational modifications including phosphorylation, ubiquitination, sumoylation … Reports also point to the involvement of p73 in regulating metabolism [ 80 ]. p73 activity is coordinated by a plethora of post-translational modifications, such as ubiquitination, phosphorylation, acetylation, or sumoylation driven by oncogenic insult or IR-mediated DNA damage [ 81 ]. …

Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.

Degenerative skeletal diseases, including osteoporosis, osteoarthritis, and intervertebral disc degeneration, are prevalent age-related conditions characterized by progressive tissue degeneration and functional decline. Histone modifications are covalent modifications of histone residues, catalyzed by specific enzymes, that modulate chromatin architecture and transcriptional activity. Accumulating evidence highlights the critical involvement of histone modifications in orchestrating disease-associated transcriptional programs. In osteoporosis, histone modifications regulate osteoblast and oste

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… Moreover, other modifications with limited investigation but experimental validation have also been reported, including citrullination, SUMOylation, ADP-ribosylation, and biotinylation [ 32 ] ( Fig. 1 ). … 87 ] Glutarylation | 2019 | KAT2A | SIRT7 | NA | [ 88 ] Lactylation | 2019 | P300/CBP | HDAC1-3 | Brg1 | [ 57 , 60 , 89 ] Ubiquitin-like | Ubiquitination | 1980 | RNF20/40; PRC1(Ring1B); BRCA1/BARD1 | USP16, 22; PR-DUB(BAP1) | PRC2(Jarid2, AEBP2); RYBP; 53BP1; DNMT1 | [ [90] , [91] , [92] , [93] ] SUMOylation …

The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

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… These modifications encompass phosphorylation, acetylation, ubiquitination, and sumoylation. KLF5 phosphorylation enhances its activity, whereas KLF5 ubiquitination diminishes its protein levels; the roles of acetylation and sumoylation are contingent upon context [ 45 ] . …

RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.

In the last decades, colorectal cancer (CRC) has emerged as a global problem, representing approximately 10% of all malignant tumors and the second leading cause of cancer-related death. Colitis-associated cancer (CAC) arises from chronic unresolved inflammation and is typically characterised by poor prognosis. Among key cellular regulators, the small GTPase RHOA controls cytoskeleton dynamics in various cell types and, thereby, key biological processes. Although it has been linked to various diseases, the role of RHOA in cancer remains controversial. RHOA has been proposed as a biomarker in c

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… | CRC | Cell migration | ( 149 ) LARG | CRC | Tumor suppressor | ( 150 ) GAPs | DLC1 | CRC (advanced stages) | Downregulation leads to cell proliferation, migration and metastases | ( 151 ) p190GAP/GAP5 | • CAC • Metastatic CRC | • Cell cycle progression • EMT and invasion | ( 152 ) ( 153 ) GDIs | Sumoylated … Post-translational modifications further modulate GDI function: GDI1 sumoylation enhances RHOA binding and reduces cancer cell motility, whereas inhibition of this modification by XIAP decreases migration in CRC cells ( 155 ). …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

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… of two hexanucleotide sequences separated by a variable number of spacer sequences. 14 In addition, NRs can be indirectly recruited to the genome by tethering mechanisms by other DNA-bound transcription factors. 15 Several posttranslational modifications, such as phosphorylation, ubiquitination and SUMOylation … Ligand binding can either stabilize or destabilize NRs by inducing conformational changes that influence ubiquitination. 339 , 340 In addition, posttranslational modifications (PTMs), such as phosphorylation, 341 SUMOylation 342 and acetylation, 343 modify NR degradation rates by altering their interaction …

PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivi

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… The transcriptional activity of PPAR-γ is modulated by various post-translational modifications, including SUMOylation and O-GlcNAcylation. … As demonstrated by Shimizu et al., SUMOylation of Lys107 negatively regulates the transcription of PPAR-γ target genes by repressing the ligand-independent transactivation function of the A/B domain, thereby reducing the overall transactivating competence of PPAR-γ [ 184 ]. …

Epigenetics in myeloproliferative neoplasms.

The myeloproliferative neoplasms (MPNs) are a group of acquired clonal disorders where mutations drive proliferative disease resulting in increased blood counts and in some cases end-stage myelofibrosis. Epigenetic changes are the reversible modifications to DNA- and RNA-associated proteins that impact gene activity without changing the DNA sequence. This review summarizes mechanisms of epigenetic changes and the nucleosome. The drivers and epigenetic regulators in MPNs are outlined. In MPNs, distinct patterns of epigenetic dysregulation have been seen in chronic and in advanced phases. Methyl

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… Other histone posttranslational modifications including butyrylation and sumoylation ( 4 ) are increasingly recognized, but their relevance in MPN is unclear and they will not be discussed in this review. Figure 1 The structure of the nucleosome. …