A Molecular Signature of the Ubiquitin-Proteasome System for Forecasting Prognosis in Thyroid Carcinoma Patients DOI Creative Commons
Hong Zeng,

Xitong Geng,

Hao Wan

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 10397 - 10419

Опубликована: Дек. 1, 2024

Background: The ubiquitin-proteasome system (UPS) is vital for protein quality control and its dysregulation linked to diseases, including cancer. Targeting the UPS becoming a promising approach in cancer therapy. However, role of modulation thyroid carcinoma (THCA) remains be fully elucidated. Methods: Initially, we utilized data from Cancer Genome Atlas (TCGA) database employ weighted gene co-expression network analysis (WGCNA) with LASSO regression develop prognostic model core genes implicated THCA. Subsequently, stratified THCA training set into two distinct subtypes based on score (UPS-PMS) characteristics. Key within were then subjected functional analysis, immunotherapy evaluation, drug sensitivity studies. Results: We delineated comprising six genes, which subsequently demonstrated was capable forecasting patient prognosis. Moreover, our findings indicated substantial correlation between UPS-PMS immune microenvironmental factors, notably negative myeloid cells potential influence Th1 Th2 ratio. Especially, observed significant association high an immunosuppressive microenvironment. Then, elucidated biological distinctions among various sample subtypes, highlighting that cluster_1 subtype associated unfavorable Of note, KCNA1 identified as pivotal framework. constructed three-tiered regulatory centered KCNA1-related competing endogenous RNA (ceRNA). Furthermore, results suggested has target immunotherapeutic strategies. Concurrently, analyses expression promoted gemcitabine resistance patients, while knockdown increased gemcitabine. Conclusion: In conclusion, developed novel UPS-based THCA, key KCNA1, assessed sensitivity, revealing new therapeutic targets. Keywords: system, carcinoma, model, microenvironment,

Язык: Английский

Proteasomal Dysfunction in Cancer: Mechanistic Pathways and Targeted Therapies DOI
Pranit Hemant Bagde, Meenakshi Kandpal, Annu Rani

и другие.

Journal of Cellular Biochemistry, Год журнала: 2025, Номер 126(1)

Опубликована: Янв. 1, 2025

ABSTRACT Proteasomes are the catalytic complexes in eukaryotic cells that decide fate of proteins involved various cellular processes an energy‐dependent manner. The proteasomal system performs its function by selectively destroying labelled with small protein ubiquitin. Dysfunctional activity is allegedly clinical disorders such as cancer, neurodegenerative disorders, ageing, and so forth, making it important therapeutic target. Notably, compared to healthy cells, cancer have a higher homeostasis requirement faster turnover rate. ubiquitin‐proteasome (UPS) helps increase rapidly experience less apoptotic cell death. Therefore, understanding UPS essential design discover some effective inhibitors for therapy. Hereby, we focused on role 26S proteasome complex, mainly UPS, carcinogenesis seeking potential targets treating numerous cancers.

Язык: Английский

Процитировано

0
Portrait of WWP1: the current state in human cancer DOI Creative Commons

Jiaming Lei,

Jun Chen,

Wenwen Yu

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 30, 2025

WWP1, a member of the C2-WW-HECT E3 ligase family, is an ubiquitin-protein containing WW domains. This enzyme plays critical role in regulating diverse cellular processes. Its expression modulated by various factors and non-coding RNAs, resulting ubiquitination that affects substrate protein degradation. WWP1 demonstrates dual function, acting predominantly as oncogene tumors but occasionally tumor suppressor. review summarizes WWP1’s biological roles, therapeutic potential oncology, upstream regulatory factors, downstream substrates. It aims to promote research on antitumor effects, improve understanding its tumorigenesis, support development targeted therapies.

Язык: Английский

Процитировано

0
Characterization of isolated human astrocytes from aging brain DOI Creative Commons
Geidy E. Serrano, Sidra Aslam, Jessica E. Walker

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

ABSTRACT Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain’s internal milieu eventually impact neuronal function leads neurodegeneration. Until now most of evidence astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by laser capture or cell cultures derived animal models lines. In this study we used postmortem-derived cells sorted anti-GFAP antibodies compare unbiased, whole-transcriptomes human control, older non-impaired individuals subjects different neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s (ADD) progressive supranuclear palsy (PSP). We found hundreds dysregulated genes between control astrocytes. addition, identified numerous shared these common disorders are similarly dysregulated; particular, UBC a gene for ubiquitin, which protein integral cellular critically important regulating outcomes proteins under stress, was upregulated PSP, PD, ADD when compared control.

Язык: Английский

Процитировано

0
Discovery of new non-symmetrical heterocyclic Pentanoid derivatives targeting metastatic triple-negative breast Cancer DOI
Khor Poh Yen, Johnson Stanslas, Nurulfazlina Edayah Rasol

и другие.

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2025, Номер unknown, С. 130232 - 130232

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
DEGRADATOR: A Gaming Expedition Into Targeted Protein Degradation Therapies DOI
Natalia A. Szulc,

Anna Olchowik,

Patrycja Jaszczak

и другие.

Journal of Chemical Education, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

In an era of rapid scientific advancement, the need for engaging educational tools is critical. DEGRADATOR, a 2D computer game, bridges this gap by immersing players in ubiquitin-proteasome system, key pathway cellular protein degradation. Designed aged 12 and above, DEGRADATOR introduces molecular mechanics targeted degradation, including PROTAC drugs. Through 10 levels gameplay combined with quizzes, it represents first-ever resource its kind to make advanced topic accessible amusing. The game was evaluated 97 high school students (age 15–19) during biology classes. Over 75% completed under 30 min, 63% rated highly (4 or 5 out 5) ability enhance their understanding 59% scored more points on final test, indicating substantial knowledge retention. Teachers highlighted game's potential deepening students' comprehension recommended accompanying materials maximize impact. By blending entertainment education, demystifies complex processes, serving as tool popularizing science addressing misconceptions surrounding new therapeutic technologies. Freely available at https://degradator-game.com, complemented teacher resources multimedia materials, ensuring broad applicability. This innovative platform not only supports classroom learning but also fosters curiosity beyond traditional academic settings.

Язык: Английский

Процитировано

0
Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System DOI Open Access
Ashok N. Hegde,

Logan E. Timm,

Connor J. Sivley

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 966 - 966

Опубликована: Янв. 24, 2025

Ubiquitin–proteasome-mediated proteolysis post-translationally regulates the amounts of many proteins that are critical for normal physiology central nervous system. Research carried out over last several years has revealed a role components ubiquitin–proteasome pathway (UPP) in neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. Studies have also shown UPP mental disorders schizophrenia autism. Even though dysregulation protein degradation by is contributory factor to pathology underlying system disorders, association between these far from simple. In this review, we discuss connections some major diseases.

Язык: Английский

Процитировано

0
Lycobetaine Has Therapeutic Efficacy in Lung Squamous Cell Carcinoma by Targeting USP32 to Trigger Ferroptosis DOI Creative Commons
Shangping Xing, Hua Chai, Zhenlong Chen

и другие.

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(3), С. 163 - 163

Опубликована: Фев. 27, 2025

Ubiquitin-specific protease 32 (USP32), a deubiquitylating enzyme that controls the ubiquitin process, is overexpressed in multiple cancers and serves as promising therapeutic target for cancer therapy. Drugs targeting ferroptosis have exhibited anticancer activity. Lycobetaine (LBT), natural alkaloid, holds promise against various cancers, yet its specific targets mechanisms remain unclear. In this study, we show LBT induced lung squamous cell carcinoma (LUSC) cells, accompanied by glutathione depletion accumulation of lipid peroxidation, malondialdehyde, ferrous iron. Mechanistically, drug affinity responsive stability-based mass spectrometry analysis, molecular dynamics simulations, cellular thermal shift assay confirmed USP32 potential LUSC cells. Moreover, strong interaction between nuclear factor erythroid 2-related 2 (NRF2) was found via immunoprecipitation–mass co-immunoprecipitation. addition, ubiquitination results demonstrated treatment significantly increased NRF2 degradation USP32. Importantly, overexpression effectively attenuated effects on proliferation orthotopic xenografts, administration inhibited tumor growth metastasis USP32–NRF2 signaling axis. Taken together, these data suggest exerts inhibiting USP32-mediated deubiquitination to induce may serve prospective USP32-targeting agent treatment.

Язык: Английский

Процитировано

0
PSMD11 and PSMD14 may serve as novel biomarkers for the prognosis of pancreatic ductal adenocarcinoma DOI Creative Commons

Yanhui Yang,

Xing Zhao, Hao Wang

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Март 20, 2025

Background The ubiquitin proteasome system is involved in the regulation of cellular gene transcription and receptor function through degradation proteins, thus affecting tumorigenesis development. In this study, bioinformatics analysis revealed expression PSMD11 PSMD14 pancreatic ductal adenocarcinoma, which can be used as biomarkers for prognosis patients with PDAC. This study provides new targets prognostic assessment targeted therapy adenocarcinoma. Methods levels value adenocarcinoma were analyzed using GEPIA2, GEO, TCGA GTEx databases, relationships between these clinical case data survival analyzed. effects on malignant biological behaviors cancer cells, such proliferation, migration invasion, investigated by vitro experiments. Results Bioinformatics that mRNAs significantly higher (PDAC) tissues than normal high was correlated a poor Further evaluation correlation results characteristics PDAC associated lymph node metastasis, TNM grade, degree differentiation, Knockdown inhibited migration, invasion ability cells. Conclusion are highly expressed malignancy adenocarcinoma; thus, potential therapeutic patients.

Язык: Английский

Процитировано

0
E3 ubiquitin ligases and their therapeutic potential in disease Management DOI
Geet Madhukar, Md Azizul Haque, Shawez Khan

и другие.

Biochemical Pharmacology, Год журнала: 2025, Номер unknown, С. 116875 - 116875

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Characterization of Isolated Human Astrocytes from Aging Brain DOI Open Access
Geidy E. Serrano, Sidra Aslam, Jessica E. Walker

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3416 - 3416

Опубликована: Апрель 5, 2025

Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain's internal milieu eventually impact neuronal function lead neurodegeneration. Until now, most evidence of astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by laser capture, or cell cultures derived animal models lines. In this study, we used postmortem-derived cells sorted anti-GFAP antibodies compare unbiased, whole-transcriptomes human control, older non-impaired individuals subjects different neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's (ADD), progressive supranuclear palsy (PSP). We found hundreds dysregulated genes between control astrocytes. addition, identified numerous shared these common disorders are similarly dysregulated; particular, UBC a gene for ubiquitin, which protein integral cellular critically important regulating outcomes proteins under stress, was upregulated PSP, PD, ADD when compared control.

Язык: Английский

Процитировано

0