Life Sciences, Journal Year: 2024, Volume and Issue: 342, P. 122512 - 122512
Published: Feb. 22, 2024
Language: Английский
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116323 - 116323
Published: Feb. 23, 2024
Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are elements of the deubiquitinase family, overexpressed in gastric (GC). Through regulation several signaling pathways, such as Wnt/β-Catenin nuclear factor-κB signaling, promotion expression deubiquitination- stabilization-associated proteins, USPs promote proliferation, metastasis, invasion, epithelial-mesenchymal transition GC. In addition, closely related to clinicopathological features, patient prognosis, chemotherapy resistance. therefore could be used prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they not yet been tested clinic. This article provides an overview latest fundamental research on GC, aiming enhance understanding how contribute GC progression, identifying possible targets treatment improve survival.
Language: Английский
Citations
10
Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)
Published: March 18, 2025
Protein quality control (PQC) plays a vital role in maintaining normal heart function, as cardiomyocytes are relatively sensitive to misfolded or damaged proteins, which tend accumulate under pathological conditions. Ubiquitin-specific protease (USP) is the largest deubiquitinating enzyme family and key component of ubiquitin proteasome system (UPS), non-lysosomal protein degradation machinery mediate PQC cells. USPs regulate stability activity target proteins that involve intracellular signaling, transcriptional inflammation, antioxidation, cell growth. Recent studies demonstrate can fibrosis, lipid metabolism, glucose homeostasis, hypertrophic response, post-ischemic recovery death such apoptosis ferroptosis cardiomyocytes. Since myocardial loss an important cardiomyopathy, therefore, these findings suggest UPSs play emerging roles cardiomyopathy. This review briefly summarizes recent literature on regulatory occurrence development giving us new insights into molecular mechanisms different cardiomyopathy potential preventive strategies for
Language: Английский
Citations
1
MedComm, Journal Year: 2024, Volume and Issue: 5(10)
Published: Sept. 25, 2024
Ubiquitination is an enzymatic process characterized by the covalent attachment of ubiquitin to target proteins, thereby modulating their degradation, transportation, and signal transduction. By precisely regulating protein quality quantity, ubiquitination essential for maintaining homeostasis, DNA repair, cell cycle regulation, immune responses. Nevertheless, diversity enzymes extensive involvement in numerous biological processes contribute complexity variety diseases resulting from dysregulation. The relies on a sophisticated system, domains, receptors, which collectively impart versatility pathway. widespread presence highlights its potential induce pathological conditions. Ubiquitinated proteins are predominantly degraded through proteasomal also plays key role localization transport, as well inflammatory pathways. This review systematically delineates roles genomic stability, cellular proliferation, Furthermore, mechanisms implicated various pathologies, alongside current modulators discussed. Enhancing our comprehension aims provide novel insights into involving propose innovative therapeutic strategies clinical
Language: Английский
Citations
8
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1303 - 1303
Published: Jan. 21, 2024
Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), also known as Parkinson’s disease protein 5, is a highly expressed in the brain. It plays an important role ubiquitin–proteasome system (UPS), where it acts deubiquitinase (DUB) enzyme. Being smallest member of UCH family DUBs, catalyzes reaction ubiquitin precursor processing and cleavage ubiquitinated remnants, thus maintaining level monomers brain cells. UCHL1 mutants, containing amino acid substitutions, influence catalytic activity its aggregability. Some them protect cells transgenic mice toxin-induced (PD) models. Studies putative partners revealed about sixty individual proteins located all major compartments cell: nucleus, cytoplasm, endoplasmic reticulum, plasma membrane, mitochondria, peroxisomes. These include related to development PD, such alpha-synuclein, amyloid-beta protein, ubiquitin-protein ligase parkin, heat shock proteins. In context paradigm, importance these interactions not clear. However, there increasing understanding that exhibits various effects catalytically independent manner through protein–protein interactions. Since this represents up 5% soluble brain, PD-related changes structure will have profound on proteomes/interactomes which involved. Growing evidence accumulating PD obviously determined by balance canonic numerous activity-independent interactions, still need better characterization.
Language: Английский
Citations
7
Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: 34(1-2), P. 17 - 49
Published: Feb. 1, 2024
Cysteine proteases are involved in a broad range of biological functions, ranging from extracellular matrix turnover to immunity. Playing an important role the onset and progression several diseases, including cancer, immune-related neurodegenerative disease, viral parasitic infections, cysteine represent attractive drug target for development therapeutic tools.
Language: Английский
Citations
7
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Jan. 22, 2024
Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate fate proteins and signaling pathway transduction by removing ubiquitin chains from target proteins. USPs are essential for modulation a variety physiological processes, such DNA repair, cell metabolism differentiation, epigenetic modulations well protein stability. Recently, extensive research has demonstrated that exert significant impact on innate adaptive immune reactions, metabolic syndromes, inflammatory disorders, infection via post-translational modification processes. This review summarizes important roles in onset progression diseases, including periodontitis, pneumonia, atherosclerosis, bowel disease, sepsis, hepatitis, diabetes, obesity. Moreover, we highlight comprehensive overview pathogenesis these diseases modifications responses pave way future prospect targeted therapies diseases.
Language: Английский
Citations
6
Molecular and Cellular Probes, Journal Year: 2023, Volume and Issue: 73, P. 101944 - 101944
Published: Dec. 4, 2023
Ubiquitin specific protease 5 (USP5) is a vital deubiquitinating enzyme that regulates various physiological functions by removing ubiquitin chains from target proteins. This review provides an overview of the structural and functional characteristics USP5. Additionally, we discuss role USP5 in regulating diverse cellular processes, including cell proliferation, apoptosis, DNA double-strand damage, methylation, heat stress, protein quality control, targeting different substrates. Furthermore, describe involvement several pathological conditions such as tumors, pain, developmental abnormalities, inflammatory diseases, virus infection. Finally, introduce newly developed inhibitors In conclusion, investigating novel substrates USP5, elucidating underlying mechanisms USP5-substrate interactions, intensifying development inhibitors, exploring upstream regulatory detail can provide new theoretical basis for treatment cancer, which promising research direction with considerable potential. Overall, plays critical its may have significant implications therapeutic strategies cancer other diseases.
Language: Английский
Citations
12
Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11
Published: Aug. 12, 2024
Metabolic disorders include obesity, nonalcoholic fatty liver disease, insulin resistance and type 2 diabetes. It has become a major health issue around the world. Ubiquitin-proteasome system (UPS) is essential for nearly all cellular processes, functions as primary pathway intracellular protein degradation. Recent researches indicated that dysfunctions in UPS may result accumulation of toxic proteins, lipotoxicity, oxidative stress, inflammation, resistance, which contribute to development progression metabolic disorders. An increasing body evidence indicates specific dietary polyphenols ameliorate by preventing lipid synthesis transport, excessive hyperglycemia through regulation UPS. This review summarized latest research progress natural improving regulating accumulation, In addition, possible mechanisms UPS-mediated prevention are comprehensively proposed. We aim provide new angle utilization
Language: Английский
Citations
4
Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)
Published: Sept. 7, 2023
Abstract An essential protein regulatory system in cells is the ubiquitin-proteasome pathway. The substrate modified by ubiquitin ligase (E1-E2-E3) this pathway, which a dynamic bidirectional modification regulation system. Deubiquitinating enzymes (DUBs) are tasked with specifically hydrolyzing molecules from ubiquitin-linked proteins or precursor and inversely regulating degradation, turn affects function. ubiquitin-specific peptidase 32 (USP32) level associated cell cycle progression, proliferation, migration, invasion, other cellular biological processes. It an important member of protease family. thought that USP32, unique enzyme controls process, closely linked to onset progression many cancers, including small lung cancer, gastric breast epithelial ovarian glioblastoma, gastrointestinal stromal tumor, acute myeloid leukemia, pancreatic adenocarcinoma. In review, we focus on multiple mechanisms USP32 various tumor types show stability distinct proteins. Therefore, key promising therapeutic target for therapy, could provide new insights avenues antitumor drug development. importance cancer treatment remains be further proven. conclusion, there options future direction research.
Language: Английский
Citations
10
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 14, 2025
HCC is characterized by a high interstitial fluid pressure (HIFP) environment, which appears to support cancer cell survival. However, the mechanisms behind this phenomenon are not fully understood. This study investigates role of kinesin family member 11 (KIF11) in under HIFP conditions, using both vivo and vitro models. In experiments replicated environment observe changes behavior protein expression, while studies involved mice portal hypertension create an orthotopic liver model, allowing for evaluation tumor progression. Additionally, clinical samples from patients were analyzed consistency with experimental findings. Results demonstrated that significantly increased proliferation, invasion, metastasis cells. Omics analysis subsequent molecular validation revealed KIF11 levels markedly upregulated HIFP, despite no significant change mRNA levels. Further investigation showed upregulation was linked reduction KIF11's ubiquitin-mediated degradation, suggesting stabilizes expression inhibiting its degradation pathway. Co-immunoprecipitation proteomic identified ubiquitin-specific peptidase 1 (USP1) as crucial factor process, deubiquitinating at K77 site, thus stabilizing Clinical confirmed USP1 overexpressed hypertension, strong correlation between two. Inhibition ML323 reduced suppressed progression mouse model. These findings suggest fosters through USP1-mediated stabilization KIF11, highlighting potential therapeutic target, especially hypertension.
Language: Английский
Citations
0