We conducted this research to explore the role of latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus (EBV) in modulating the DNA damage response (DDR) and its regulatory mechanisms in radioresistance. Our results revealed that LMP1 repressed the repair of DNA double strand breaks (DSBs) by inhibiting DNA-dependent protein kinase (DNA-PK) phosphorylation and activity. Moreover, LMP1 reduced the phosphorylation of AMP-activated protein kinase (AMPK) and changed its subcellular location after irradiation, which appeared to occur through a disruption of the physical interaction between AMPK and DNA-PK. The decrease in AMPK activity was associated with LMP1-mediated glycolysis and resistance to apoptosis induced by irradiation. The reactivation of AMPK significantly promoted radiosensitivity both in vivo and in vitro. The AMPKα (Thr172) reduction was associated with a poorer clinical outcome of radiation therapy in NPC patients. Our data revealed a new mechanism of LMP1-mediated radioresistance and provided a mechanistic rationale in support of the use of AMPK activators for facilitating NPC radiotherapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.canlet.2016.05.032 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.
Proc Natl Acad Sci U S A
February 2025
Center for Medical Research and Innovation, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, Chinese Academy of Medical Sciences (RU069), Medical College of Fudan University, Shanghai 201399, China.
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.
View Article and Find Full Text PDFAMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage.
Proc Natl Acad Sci U S A
February 2025
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114.
Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, DOX toxicity and AMH rescue mechanisms in the ovary have remained unclear. Herein, we characterize the consequences of these treatments in ovarian cell types using scRNAseq.
View Article and Find Full Text PDFReactions to disclosed biofeedback information on skin DNA damage in individuals after a beach holiday: a mixed methods intervention study.
Photochem Photobiol Sci
January 2025
Department of Prevention and Information, Danish Cancer Society, Copenhagen, Denmark.
Background: The incidence of skin cancer among Danes is one of the highest in the world. Most skin cancers are, however, avoidable with sun protection and reduction of exposure. One way to increase awareness could be through personal biofeedback information about skin DNA damage.
View Article and Find Full Text PDFEvaluating the biological impact of shelters on astronaut health during different solar particle events: a Geant4-DNA simulation study.
Radiat Environ Biophys
January 2025
Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), Shiraz University of Medical Sciences, Shiraz, Iran.
Mechanistic Monte Carlo simulations have proven invaluable in tackling complex challenges in radiobiology, for example for protecting astronauts from solar particle events (SPEs) during deep space missions which remains an underexplored area. In this study, the Geant4-DNA Monte Carlo code was used to assess the DNA damage caused by SPEs and evaluate the protective effectiveness of a multilayer shelter. By examining the February 1956 and October 1989 SPEs-two extreme cases-the results showed that the proposed shelter reduced DNA damage by up to 57.
View Article and Find Full Text PDFPrepubertal phthalate exposure can cause histopathological alterations, DNA methylation and histone acetylation changes in rat brain.
Toxicol Ind Health
January 2025
Department of of Toxicology, Faculty of Pharmacy, Istanbul Okan University, Istanbul, Turkey.
Di-2-(ethylhexyl)phthalate (DEHP) is a phthalate derivative used extensively in a wide range of materials, such as medical devices, toys, cosmetics, and personal care products. Many mechanisms, including epigenetics, may be involved in the effects of phthalates on brain development. In this study, Sprague-Dawley male rats were obtained 21-23 days after their birth (post-weaning) and were exposed to DEHP during the prepubertal period with low-dose DEHP (DEHP-L, 30 mg/kg/day) and high-dose DEHP (DEHP-H, 60 mg/kg/day, 37 days) until the end of adolescence (PND 60).
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!