USP7 promotes endothelial activation to aggravate sepsis-induced acute lung injury through PDK1/AKT/NF-κB signaling pathway DOI Creative Commons
Zhiyi Liu,

Xiaoyun Shi,

Tiantian Ke

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 17, 2025

Abstract Disruption of the endothelial cell barrier and subsequent inflammatory response represent a central pathological feature acute lung injury (ALI). Ubiquitination plays pivotal role in regulating protein stability, intracellular transport, enzyme activity, which is typically reversed by deubiquitinating enzymes. Nevertheless, function enzymes biology ALI remains largely uninvestigated. The present study demonstrates that expression USP7 increased instances inflammation ALI. knockdown or inhibition using specific inhibitors was observed to significantly reduce TNF-α-induced cells their adhesion capacity monocytes. Conversely, overexpression promote cells. were found be effective mitigating induced LPS. From mechanistic perspective, our findings indicate binds deubiquitinates PDK1, thereby stabilizing PDK1 promoting activity pathway In conclusion, demonstrate novel USP7-PDK1 signaling axis vascular reveal deubiquitylating PDK1. These observations suggest targeting may offer promising therapeutic strategy for treatment injury.

Язык: Английский

Deubiquitinases as novel therapeutic targets in colorectal cancer DOI Open Access

Noor Al Shukri,

Razik Bin Abdul Momin

Asia-Pacific Journal of Oncology, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Colorectal cancer (CRC) is one of the leading causes cancer-related mortality and third most prevalent malignant tumor in world. In recent years, key role protein post-translational modifications, especially ubiquitination deubiquitination tumorigenesis progression has gradually been revealed. Deuubiquitinating Enzymes (DUBs) play an important CRC cell proliferation, apoptosis, autophagy, immune escape, chemotherapy resistance by removing ubiquitin chains from proteins, regulating stability, activity, subcellular localization. Research shown that DUBs such as USP7, USP10, USP22 promote metastasis stabilizing associated proteins β-catenin, p53, c-Myc, activating signaling pathways Wnt/β-catenin ERK/MAPK. addition, exacerbate malignancy microenvironment (TME) inflammatory responses, polarization macrophages. Meanwhile, are closely related to resistance, decreased drug sensitivity maintaining stability targets or enhancing anti-apoptotic function. At present, small molecule inhibitors targeting have made certain progress, USP7 inhibitor P5091 USP14 IU1, providing new directions for treatment CRC. However, clinical applications still face challenges selectivity safety concerns. summary, in-depth research on molecular mechanisms CRC, development more efficient specific targeted inhibitors, exploration their combined application with other therapeutic methods expected provide strategies diagnosis

Язык: Английский

Процитировано

0
The Role of the Ubiquitin System in Eye Diseases DOI Creative Commons
Sandra Carolina Durán-Cristiano, Laura de Diego‐Garcia, Alba Martín‐Gil

и другие.

Life, Год журнала: 2025, Номер 15(3), С. 504 - 504

Опубликована: Март 20, 2025

The ubiquitin–proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This responsible for the degradation of proteins, while proteasomes play significant role in mechanisms involved health human diseases. participation UPS response particularly relevant, leading to involvement immunoproteasomes. specialized proteasome processing presentation antigenic peptides, making it crucial proper function. Moreover, impact considered essential understanding several diseases, such as neurodegenerative disorders, infections, vascular dysregulation may contribute pathogenesis these conditions, highlighting its importance potential therapeutic target. Interestingly, also related ocular structures, playing visual perception homeostasis. regulation processes suggests on both anterior posterior eye pathologies. review aims discuss general considerations provide information about By disease, researchers clinicians explore novel strategies targeting treatment conditions. In conclusion, player processes, with far-reaching implications segments eye. Further research this field lead development innovative therapies better complex underlying disorders.

Язык: Английский

Процитировано

0
Unlocking the brain's code: The crucial role of post-translational modifications in neurodevelopment and neurological function DOI
Peng Ye,

Wangzheqi Zhang,

Yan Liao

и другие.

Physics of Life Reviews, Год журнала: 2025, Номер 53, С. 187 - 214

Опубликована: Март 23, 2025

Язык: Английский

Процитировано

0
Identification and validation of CDC20 and ITCH as ubiquitination related biomarker in idiopathic pulmonary fibrosis DOI Creative Commons

Shulei Sun,

Yubao Wang,

Jing Feng

и другие.

Hereditas, Год журнала: 2025, Номер 162(1)

Опубликована: Апрель 1, 2025

Abstract Purpose Ubiquitination plays a crucial role in various diseases. This study aims to explore the potential ubiquitination related genes IPF. Methods The gene microarray dataset GSE24206 was obtained from GEO database. Subsequently, through differential expression analysis and molecular signatures database, we 1734 differentially expressed 742 genes. Through venn diagram analysis, 53 Then, gene-ontology (GO) enrichment Kyoto Encyclopedia of Genes Genomes (KEGG) pathway protein-protein interactions (PPI) set (GSEA) were applied for Finally, CDC20 ITCH IPF patients cells validated by qPCR western blot assay. Results A total (36 up-regulated 17 down-regulated genes) identified between 6 healthy controls. GO KEGG mainly involved regulation protein ubiquitination, post-translational modification ubiquitin mediated proteolysis. PPI results demonstrated that these interacted with each other. GSEA some hub epithelial mesenchymal transition, inflammatory response, hypoxia, apoptosis. experiment level consistent bioinformatics results. Conclusion We analysis. other may influence development transition response. Our research findings provide insights into mechanisms fibrosis evidence therapeutic targets fibrosis.

Язык: Английский

Процитировано

0
Endothelial USP11 drives VEGFR2 signaling and angiogenesis via PRDX2/c-MYC axis DOI
Can Chen,

Zilong Chen,

Ruijie Luo

и другие.

Angiogenesis, Год журнала: 2025, Номер 28(2)

Опубликована: Апрель 8, 2025

Язык: Английский

Процитировано

0
Integrating multi-omics and experimental techniques to decode ubiquitinated protein modifications in hepatocellular carcinoma DOI Creative Commons
Haikun Yang, Yuan Chen, Zheng Zhou

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 11, 2025

Background Ubiquitination, a critical post-translational modification, plays pivotal role in regulating protein stability and activity, influencing various aspects of cancer development, including metabolic reprogramming, immune evasion, tumor progression. However, the specific ubiquitination hepatocellular carcinoma (HCC), particularly relation to microenvironment (TME), remains poorly understood. This study aims systematically explore shaping TME HCC, with focus on its impact progression modulation. Methods We performed bioinformatics analysis by integrating multiple publicly available HCC datasets assess status across cell types TME, plasma cells, fibroblasts, endothelial epithelial-mesenchymal transition (EMT) cells. Ubiquitination scores were calculated categorize these types, survival data, along spatial transcriptomics, employed evaluate how different levels influence In vitro experiments, such as transwell, CCK8, wound healing assays, used further investigate key gene UBE2C phenotypes. Results Our revealed that ubiquitination-related genes are significantly upregulated tissues, high expression correlating poor prognosis patients. Pathway showed enriched processes cycle regulation, DNA repair, p53 signaling. These pathways contribute promoting proliferation, facilitating matrix remodeling, enhancing angiogenesis. Notably, UBE2C, enzyme, appears play potentially inhibiting anti-tumor responses reducing system’s ability recognize eliminate Furthermore, experimental data confirmed overexpression promotes invasion, metastasis, supporting remodeling. Conclusion reveals multifaceted regulatory roles HCC. not only supports proliferation anti-apoptotic functions within cells but also modulating activity stromal Among all genes, emerges potential prognostic biomarker therapeutic target offering new directions for precision treatment future.

Язык: Английский

Процитировано

0
USP7 promotes endothelial activation to aggravate sepsis-induced acute lung injury through PDK1/AKT/NF-κB signaling pathway DOI Creative Commons
Zhiyi Liu,

Xiaoyun Shi,

Tiantian Ke

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 17, 2025

Abstract Disruption of the endothelial cell barrier and subsequent inflammatory response represent a central pathological feature acute lung injury (ALI). Ubiquitination plays pivotal role in regulating protein stability, intracellular transport, enzyme activity, which is typically reversed by deubiquitinating enzymes. Nevertheless, function enzymes biology ALI remains largely uninvestigated. The present study demonstrates that expression USP7 increased instances inflammation ALI. knockdown or inhibition using specific inhibitors was observed to significantly reduce TNF-α-induced cells their adhesion capacity monocytes. Conversely, overexpression promote cells. were found be effective mitigating induced LPS. From mechanistic perspective, our findings indicate binds deubiquitinates PDK1, thereby stabilizing PDK1 promoting activity pathway In conclusion, demonstrate novel USP7-PDK1 signaling axis vascular reveal deubiquitylating PDK1. These observations suggest targeting may offer promising therapeutic strategy for treatment injury.

Язык: Английский

Процитировано

0