AI Article Synopsis
- PA28γ is often overexpressed in liver cancer and is linked to tumor development and HBV replication.
- The study reveals that the hepatitis B virus X protein (HBx) boosts PA28γ expression by increasing p53 levels in liver cancer cells.
- This creates a feedback loop where elevated PA28γ levels inhibit the degradation of HBx, promoting its accumulation and consequently enhancing HBV replication.
Article Abstract
Proteasomal activator gamma (PA28γ), frequently overexpressed in hepatocellular carcinoma, is believed to play important roles in tumourigenesis. However, the underlying mechanism of PA28γ overexpression and its possible roles in hepatitis B virus (HBV) replication are largely unknown. In the present study, we found that hepatitis B virus X protein (HBx) activates PA28γ expression by upregulating p53 levels in human hepatoma cells. The elevated PA28γ levels in turn repressed seven in absentia homologue 1 expression via downregulation of p53 levels, thereby inhibiting ubiquitin-dependent proteasomal degradation of HBx, which ultimately led to upregulation of HBx levels. The correlation among HBx, p53 and PA28γ was exactly reproduced in a 1.2-mer HBV replicon system, mimicking the natural course of HBV infection. In particular, knockdown of either p53 or PA28γ in HepG2 cells downregulated HBx levels and thereby inhibited HBV replication, whereas overexpression of p53 or PA28γ in Hep3B cells upregulated HBx levels, which stimulated HBV replication, indicating that p53 and PA28γ act as activators of HBV replication. In conclusion, HBx levels are upregulated via a positive feedback loop involving p53 and PA28γ to stimulate HBV propagation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1099/jgv.0.001054 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Injectable DAT-ALG Hydrogel Mitigates Senescence of Loaded DPMSCs and Boosts Healing of Perianal Fistulas in Crohn's Disease.
ACS Biomater Sci Eng
January 2025
Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
Perianal fistulas (PAFs) are a severe complication of Crohn's disease that significantly impact patient prognosis and quality of life. While stem-cell-based strategies have been widely applied for PAF treatment, their efficacy remains limited. Our study introduces an injectable, temperature-controlled decellularized adipose tissue-alginate hydrogel loaded with dental pulp mesenchymal stem cells (DPMSCs) for in vivo fistula treatment.
View Article and Find Full Text PDFIn p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport.
View Article and Find Full Text PDFColorectal cancer (CRC) is a prevalent and deadly disease, necessitating the exploration of novel therapeutic strategies. Traditional chemotherapy often encounters drug resistance and adverse side effects, highlighting the need for alternative approaches. , a plant rich in phytochemical constituents, was investigated for its potential as an anticancer agent against colorectal cancer (CRC).
View Article and Find Full Text PDFRecent Perspectives on Anticancer Potential of Coumarin Against Different Human Malignancies: An Updated Review.
Food Sci Nutr
January 2025
Agricultural Extension Directorate, MAAR Damascus Syria.
Coumarins, a group of naturally occurring compounds, have been reported to demonstrate anticancer potential. These substances, distinguished by their combined benzene and α-pyrone rings, have been demonstrated to impact multiple cellular mechanisms essential for the initiation and advancement of cancer. These agents work in different ways that prevent different tumor cells from growing, spreading, and increasing.
View Article and Find Full Text PDFInorganic arsenic modulates cell apoptosis by regulating Argonaute 2 expression via the p53 pathway.
Toxicol Res (Camb)
January 2025
Yunnan Provincial Key Laboratory of Public Health and Biosafety and School of Public Health, Kunming Medical University, No. 1168 Chunrongxi Road, Chenggong, Kunming, Yunnan 650500, China.
This study explores the role of Argonaute 2 (AGO2) in the induction of apoptosis by arsenic in 16HBE cells and investigates the association between AGO2 expression and arsenic exposure in a human population. By silencing AGO2 with siRNA, we examined its impact on cell viability and apoptosis using CCK-8, HO-PI, and JC-1 assays, complemented by qRT-PCR and Western blot analyses for gene and protein expressions. Our findings revealed a significant correlation between AGO2 expression and levels of exposure to inorganic arsenic (iAs), which was more pronounced than with other arsenic forms such as monomethylarsonic (MMA) and dimethylarsinic acids (DMA).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!