USP32 deubiquitinase: cellular functions, regulatory mechanisms, and potential as a cancer therapy target DOI Creative Commons
Shuang Li, Yang Song, Kexin Wang

et al.

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

Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer DOI Open Access
Kaiqiang Li, Xiao Bai,

Angting Ke

et al.

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

9
The role of ubiquitination in health and disease DOI Creative Commons

Yan Liao,

Wangzheqi Zhang,

Yang Liu

et al.

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

7
Therapeutic cysteine protease inhibitors: a patent review (2018–present) DOI

Giulia Barchielli,

Antonella Capperucci, Damiano Tanini

et al.

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

6
Ubiquitin Carboxyl-Terminal Hydrolase L1 and Its Role in Parkinson’s Disease DOI Open Access
О.А. Бунеева, A. E. Medvedev

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

5
Roles of ubiquitin-specific proteases in inflammatory diseases DOI Creative Commons
Rui Chen, Hui Zhang, Linke Li

et al.

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

5
High interstitial fluid pressure enhances USP1-dependent KIF11 protein stability to promote hepatocellular carcinoma progression DOI Creative Commons

Zhengyi Wu,

Chao Li, Shouhua Zhang

et al.

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
Five Key Criteria for Identifying Optimal Therapeutic Targets in Protein‐Mediated Diseases DOI
Mohammed Baqur S. Al‐Shuhaib, Jafar M. B. Al‐Shuhaib

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(4)

Published: Jan. 1, 2025

Abstract Therapeutic trends involve designing ligands to target proteins in various diseases, but no parallel filters have been established prioritize pathological within pathogens for optimal inhibition. This study unveils that order a protein serve as an therapeutic intervention, it must exhibit five key attributes. It should druggable site with recognized cleft which ligand can be fitted high specificity. possess unique structure, distinct sequences having low similarity other non‐targeted proteins. dispensable the pathogenesis of disease, and case microbial infection, crucial survival infectious organisms. available crystallized 3D structure enable high‐throughput screening candidate ligands. occupy accessible localization provide easy route reach its less effort. The justifies rules essential considering ideal any protein‐mediated dysfunction. When these targeting are found protein, eradicating intended ailment primarily enhanced time, money,

Language: Английский

Citations

0
USP39 promotes retinal pathological angiogenesis in retinopathy of prematurity by stabilizing SIRT2 expression through deubiquitination DOI
Xiuxian Wang, Pei‐Cheng Zhang, Jing Xie

et al.

International Ophthalmology, Journal Year: 2025, Volume and Issue: 45(1)

Published: Jan. 24, 2025

Language: Английский

Citations

0
USP7 deficiency promotes diabetic wound healing by repressing GATA3-mediated pro-inflammatory macrophage polarization DOI

Yan Zhu,

Ming Zong,

Ling Hu

et al.

Molecular and Cellular Endocrinology, Journal Year: 2025, Volume and Issue: unknown, P. 112489 - 112489

Published: Feb. 1, 2025

Language: Английский

Citations

0
BRISC inactivation alleviates alcohol-induced liver injury in mice DOI Creative Commons
Ting Wang, Wen Zhang, Xian Liu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 12, 2025

BRCC3 isopeptidase complex (BRISC) is a JAMM subfamily deubiquitinase that has been revealed to be required for optional activation of NLRP3 inflammasome and TLR4/NF-κB signaling pathway. BRISC plays an important role in lipopolysaccharide (LPS)/D-galactosamine-induced acute liver failure, while its functional contribution alcoholic disease (ALD) still unclear. In this study, we found the expression components was increased tissues hepatitis (AH) animal models patients with AH. Mice lacking either scaffold subunit ABRO1 or catalytic showed attenuated steatosis, inflammation, injury compared control mice after chronic plus binge ethanol feeding. Moreover, pharmacological inhibition activity by inhibitor thiolutin potently protected from ALD development. Preliminary mechanistical studies deficiency did not directly affect alcohol-induced hepatocyte translocation LPS through damaged gut mucosa feeding, but prevented liver. Collectively, our work previously unknown suggested may serve as promising therapeutic target treatment.

Language: Английский

Citations

0