A Novel Approach to Explore Metabolic Diseases: Neddylation DOI Creative Commons
Huiwen Ren, Zhilin Luan, Ruijing Zhang

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 210, P. 107532 - 107532

Published: Dec. 1, 2024

Protein post translational modification (PTM) is the main regulatory mechanism for eukaryotic cell function, among which ubiquitination based on reversible degradation of proteins by ubiquitin proteasome system to regulate homeostasis. The neural precursor expressed developmental downregulated gene 8 (NEDD8) a kind like protein that shares 80 % homology and 60 identity with ubiquitin. PTM process covalently binding NEDD8 lysine residues in called neddylation. neddylation reaction could be regulated NEDD8, its precursors, substrates, E1 activating enzymes, E2 E3 ligases, de-neddylases, inhibitors, such as MLN4924. widely whole structure multiple tissues species, related factors are highly metabolism adrenal glands, thyroid parathyroid skeletal muscles, myocardium, adipose tissues, metabolic cardiovascular, cerebrovascular liver diseases, adipogenic osteogenic differentiation, well tumor glycolysis glucose resulting from angiogenesis endothelial disfunction, hepatotoxicity, adipogenesis, osteogenesis, Warburg effect, insulin function. This review provides researchers new approach explore diseases via searching analyzing histological, cytological, subcellular localization specific molecules databases, exploring mediating terms development pre-clinical pharmacological inhibitors.

Language: Английский

Protein neddylation and its role in health and diseases DOI Creative Commons
Shizhen Zhang, Qing Yu, Zhijian Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 4, 2024

Abstract NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like that covalently attached to a lysine residue of substrate through process known as neddylation, catalyzed by the enzyme cascade, namely activating (E1), conjugating (E2), and ligase (E3). The substrates neddylation are categorized into cullins non-cullin proteins. Neddylation activates CRLs (cullin RING ligases), largest family E3 ligases, whereas alters their stability activity, well subcellular localization. Significantly, pathway and/or many abnormally activated or over-expressed in various human diseases, such metabolic disorders, liver dysfunction, neurodegenerative cancers, among others. Thus, targeting becomes attractive strategy for treatment these diseases. In this review, we first provide general introduction on its biochemical regulation, crystal structures enzymes complex with cullin substrates; then discuss how governs key biological processes via modification substrates. We further review literature data dysregulated several particularly cancer, followed outline current efforts discovery small molecule inhibitors promising therapeutic approach. Finally, few perspectives were proposed extensive future investigations.

Language: Английский

Citations

36
Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer DOI Creative Commons
Pathea Bruno,

Aneeta Arshad,

Maria-Raluca Gogu

et al.

Life, Journal Year: 2025, Volume and Issue: 15(1), P. 126 - 126

Published: Jan. 18, 2025

Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations environmental stressors, on one hand, cancer cell structure, functioning, behavior. Aberrant PTMs can be considered as enabling characteristics long they orchestrate all malignant variability in proteome cells, cancer-associated tumor microenvironment (TME). On other enhance anticancer mechanisms tumoral ecosystem or sustain beneficial effects oncologic therapies through degradation inactivation carcinogenic or/and activation tumor-suppressor proteins. In this review, we summarized analyzed a wide spectrum involved regulatory that drive tumorigenesis, genetic instability, epigenetic reprogramming, events metastatic cascade, cytoskeleton extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, metabolism rewiring most important hallmarks cancer. All develop due to proteins, which modulate gene transcription, intracellular signaling, protein size, activity, stability localization, trafficking, secretion, half-life, protein–protein interactions (PPIs). associated with exploited better understand underlying molecular heterogeneous chameleonic disease, find new biomarkers progression prognosis, personalize oncotherapies, discover targets for drug development.

Language: Английский

Citations

2
Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential DOI Creative Commons
Jan Jakub Lica, Bhaskar Pradhan, Kawthar Safi

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(17), P. 4280 - 4280

Published: Sept. 9, 2024

In this review we explore innovative approaches in the treatment of hematologic cancers by combining various therapeutic modalities. We discuss synergistic potential inhibitors targeting different cellular pathways with immunotherapies, molecular therapies, and hormonal therapies. Examples include PI3K proteasome inhibitors, NF-κB immunotherapy checkpoint neddylation therapies tumor microenvironment. Additionally, use small molecules peptide cancer treatment. These multidimensional combinations present promising strategies for enhancing efficacy overcoming resistance mechanisms. However, further clinical research is required to validate their effectiveness safety profiles patients.

Language: Английский

Citations

6
Pan-cancer analysis unveils the role and mechanisms of neddylation modifications in tumorigenesis DOI

Qin Hu,

Xiang Li,

Ping Wang

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 19, 2025

Language: Английский

Citations

0
Multi-omics Analysis Revealed the Diagnostic and Therapeutic Value of Immunogenic Cell Death-derived SCN5A in Hepatocellular Carcinoma DOI

Zicheng Liang,

Wei Tan, Xiangdong Fang

et al.

Molecular Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

Citations

0
Evaluating the Role of Neddylation Modifications in Kidney Renal Clear Cell Carcinoma: An Integrated Approach Using Bioinformatics, MLN4924 Dosing Experiments, and RNA Sequencing DOI Creative Commons
Dequan Liu, Guangzhen Wu, Shijin Wang

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 635 - 635

Published: May 15, 2024

Background: Neddylation, a post-translational modification process, plays crucial role in various human neoplasms. However, its connection with kidney renal clear cell carcinoma (KIRC) remains under-researched. Methods: We validated the Gene Set Cancer Analysis Lite (GSCALite) platform against The Genome Atlas (TCGA) database, analyzing 33 cancer types and their link 17 neddylation-related genes. This included examining copy number variations (CNVs), single nucleotide (SNVs), mRNA expression, cellular pathway involvement, methylation. Using Variation (GSVA), we categorized these genes into three clusters examined impact on KIRC patient prognosis, drug responses, immune infiltration, oncogenic pathways. Afterward, our objective is to identify that exhibit overexpression are associated an adverse prognosis. After pinpointing specific target gene, used inhibitor MLN4924 inhibit neddylation conduct RNA sequencing related vitro experiments verify study specificity potential mechanisms target. approach geared towards enhancing understanding of prognostic importance KIRC. Results: identified significant CNV, SNV, methylation events across cancers, notably higher expression levels observed Cluster analysis revealed trade-off interactions among genes, where both high low gene linked prognoses. association particularly pronounced concerning lymph node T stage classification, Fustat score. Simultaneously, research discovered PSMB10 exhibits when compared normal tissues, negatively impacting Through assays, confirmed inhibition could play regulation signaling pathways, thereby influencing prognosis Moreover, results underscore as viable for therapeutic intervention KIRC, opening up novel pathways development targeted treatment strategies. Conclusion: underscores regulatory function mechanism phenotype identifying key

Language: Английский

Citations

3
MLN4924 alleviates autoimmune myocarditis by promoting Act1 degradation and blocking Act1-mediated mRNA stability DOI Creative Commons

Zuli Jiang,

Zhuolun Li, Youming Chen

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 139, P. 112716 - 112716

Published: July 21, 2024

Prolonged exposure to interleukin-17A (IL-17A) can induce autoimmune myocarditis, and MLN4924, an inhibitor of NEDD8 activating enzyme (NAE), has been reported effectively suppress various inflammatory reactions. However, the effects MLN4924 in IL-17A-mediated inflammation associated with myocarditis remain uncertain.

Language: Английский

Citations

2
Structural diversity of the CE-clan proteases in bacteria to disarm host ubiquitin defenses DOI Creative Commons
Lucía Sánchez-Alba,

Helena Borràs-Gas,

Ge Huang

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

1
The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors DOI
Qihai Sui,

Huiqiang Yang,

Zhengyang Hu

et al.

Pharmaceutical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Language: Английский

Citations

1
Neddylation-related gene signature predicts the prognosis and is associated with immune infiltration of glioma DOI Creative Commons
Zhipeng Jiang, Wen Yin, Guihua Tang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 8, 2024

Abstract Background Glioma is the most prevalent malignant tumor that originates from central nervous system. Neddylation, a post-translational modification similar to ubiquitination, involved in tumorigenesis and progression. However, there were limited studies focused on neddylation glioma. Therefore, we aimed explore potential role of Methods In this study, neddylation-related genes (NRGs) identified used construct prognostic signature for glioma patients. Based index, also explored differences clinical features, mutational landscape, immune cell infiltration between high-risk low-risk groups. Next, single-cell RNA sequencing analysis was further performed verify expression these NRG signature. At last, one gene selected validated by vitro experiments. Results Seven (TOP2A, F2R, UST, HSPA1B, LGALS3BP, UROS, OSBPL11) signature, which able successfully classify patients into A nomogram based other factors developed accurately predict prognosis Significant prognosis, found distinct Moreover, experiments illustrated knockdown HSPA1B could inhibit proliferation, migration, invasion cells polarization M2 macrophages. Conclusion These findings provide new insights understanding relationship NRGs development identify novel biomarkers may help guiding precise treatments

Language: Английский

Citations

0