ArticleCancer science2015
Celastrol induces proteasomal degradation of FANCD2 to sensitize lung cancer cells to DNA crosslinking agents.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Upregulation of Ferroptosis-Related Fanconi Anemia Group D2 is a Poor Prognostic Factor and an Indicator of Tumor Immune Cell Infiltration in Lung Adenocarcinoma.Frontiers in genetics · 2022Article
- Review
- Comprehensive Analysis of Ferroptosis Regulators in Lung Adenocarcinomas Identifies Prognostic and Immunotherapy-Related Biomarkers.Frontiers in molecular biosciences · 2021Article
- Ferroptosis-Related Genes in Lung Adenocarcinoma: Prognostic Signature and Immune, Drug Resistance, Mutation Analysis.Frontiers in genetics · 2021Article
- Screening of a Focused Ubiquitin-Proteasome Pathway Inhibitor Library Identifies Small Molecules as Novel Modulators of Botulinum Neurotoxin Type A Toxicity.Frontiers in pharmacology · 2021Article
- Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells.Frontiers in oncology · 2020Review
- Celastrol-induced degradation of FANCD2 sensitizes pediatric high-grade gliomas to the DNA-crosslinking agent carboplatin.EBioMedicine · 2019Article
- MTDH/AEG-1 downregulation using pristimerin-loaded nanoparticles inhibits Fanconi anemia proteins and increases sensitivity to platinum-based chemotherapy.Gynecologic oncology · 2019Article
- Celastrol pretreatment as a therapeutic option against cisplatin-induced nephrotoxicity.Toxicology research · 2019Article
- Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer.Free radical research · 2019Article
- Expression of FANCD2 is associated with prognosis in patients with nasopharyngeal carcinoma.International journal of clinical and experimental pathology · 2019Article
- Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR.Oncotarget · 2017Article
- Optimization on biodistribution and antitumor activity of tripterine using polymeric nanoparticles through RES saturation.Drug delivery · 2017Article
- Celastrol inhibits migration and invasion through blocking the NF-κB pathway in ovarian cancer cells.Experimental and therapeutic medicine · 2017Article
- Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases.Frontiers in medicine · 2017Review
- Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT Oncoprotein in t(8;21) Leukemia.Molecules (Basel, Switzerland) · 2016Article
- Low-Dose Celastrol Modulates IL-6 Secretion to Overcome Resistance to Sorafenib in Hepatocellular Carcinoma Cells.Iranian journal of pharmaceutical research : IJPRArticle
- Effects of Sepantronium Bromide (YM-155) on the Whole Transcriptome of MDA-MB-231 Cells: Highlight on Impaired ATR/ATM Fanconi Anemia DNA Damage Response.Cancer genomics & proteomicsArticle
- Advances in the understanding of Fanconi Anemia Complementation Group D2 Protein (FANCD2) in human cancer.Cancer cell & microenvironmentArticle
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Fanconi anemia (FA) pathway plays a key role in interstrand crosslink (ICL) repair and maintenance of the genomic stability, while inhibition of this pathway may sensitize cancer cells to DNA ICL agents and ionizing radiation (IR). The active FA core complex acts as an E3 ligase to monoubiquitinate FANCD2, which is a functional readout of an activated FA pathway. In the present study, we aimed to identify FANCD2-targeting agents, and found that the natural compound celastrol induced degradation of FANCD2 through the ubiquitin-proteasome pathway. We demonstrated that celastrol downregulated the basal and DNA damaging agent-induced monoubiquitination of FANCD2, followed by proteolytic degradation of the substrate. Furthermore, celastrol treatment abrogated the G2 checkpoint induced by IR, and enhanced the ICL agent-induced DNA damage and inhibitory effects on lung cancer cells through depletion of FANCD2. These results indicate that celastrol is a FANCD2 inhibitor that could interfere with the monoubiquitination and protein stability of FANCD2, providing a novel opportunity to develop FA pathway inhibitor and combinational therapy for malignant neoplasms.
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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.