ArticleFrontiers in oncology2021
The Valproate Mediates Radio-Bidirectional Regulation Through RFWD3-Dependent Ubiquitination on Rad51.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Ubiquitin's code: UPS orchestrating DNA repair and genomic stability under genotoxic stress.Molecular and cellular biochemistry · 2026Review
- Macrophage polarization regulated by the βTrCP-NF-κB inflammatory signaling pathway is required for valproic acid's dual role in breast tumor radiosensitivity and normal tissue radioprotection.Frontiers in immunology · 2026Article
- Reposition of lenalidomide as a radiation protector based on LINCS gene expression signatures and its preclinical validation.Scientific reports · 2025Article
- GAPDH facilitates homologous recombination repair by stabilizing RAD51 in an HDAC1-dependent manner.EMBO reports · 2023Article
- Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation.International journal of molecular sciences · 2023Review
- VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU.Cell death & disease · 2023Article
- Valproic acid as a radio-sensitizer in glioma: A systematic review and meta-analysis.Neuro-oncology practice · 2023Article
- Screen identifies fasudil as a radioprotector on human fibroblasts.Toxicology research · 2022Article
- Valproic Acid Regulates HR and Cell Cycle Through MUS81-pRPA2 Pathway in Response to Hydroxyurea.Frontiers in oncology · 2021Article
- RFWD3: A pivotal E3 ubiquitin ligase in DNA damage response, non-neoplastic disorders and multi-system tumorigenesis.Science progressReview
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ionizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related to the increase of its ubiquitination regulated by E3 ligase RFWD3 for the radiosensitization, which was opposite to normal cells, indicating that RFWD3-dependent ubiquitination on Rad51 was involved in the VPA-mediated radio-bidirectional effect. Through DMBA-transformed breast cancer rat model, VPA at 200 mg/kg radiosensitized tumor tissue cells by increasing RFWD3 and inhibited Rad51, while radioprotected normal tissue cells by decreasing RFWD3 and enhanced Rad51. In addition, we found high-level Rad51 was associated with tumorigenesis and poor prognosis in breast cancer patients. Our findings uncovered RFWD3-dependent Rad51 ubiquitination was the novel mechanism of VPA-mediated radio-bidirectional effect, VPA is a potential adjuvant treatment for tumor RT.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.