ArticleThe Journal of biological chemistry2013
Phosphorylation of ribosomal protein S3 and antiapoptotic TRAF2 protein mediates radioresistance in non-small cell lung cancer cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 68 citations in OpenAlex.
- Ribosomal protein S3: a critical regulator of human disease mechanisms.Bioscience reports · 2026Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Integrating Single-Cell, Bulk, and Spatial Transcriptomics Unveils a Novel Ribosome Biogenesis-Related Prognostic Model and DefinesInternational journal of molecular sciences · 2026Article
- Extra-Ribosomal Roles for Ribosomal Proteins and Their Relevance to Tumour Suppression, Carcinogenesis and Cancer Progression.Cancers · 2025Review
- RBIS regulates ribosome biogenesis to affect progression in lung adenocarcinoma.Journal of translational medicine · 2024Article
- Ribosomal rodeo: wrangling translational machinery in gynecologic tumors.Cancer metastasis reviews · 2024Review
- SEC14L3 knockdown inhibited clear cell renal cell carcinoma proliferation, metastasis and sunitinib resistance through an SEC14L3/RPS3/NFκB positive feedback loop.Journal of experimental & clinical cancer research : CR · 2024Article
- Proteomics shows that brain metastases of lung adenocarcinoma overexpress ribosomal proteins in response to gamma knife radiosurgery.Scientific reports · 2024Article
- Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma.Haematologica · 2024Article
- Generation and Characterization of Trastuzumab/Pertuzumab-Resistant HER2-Positive Breast Cancer Cell Lines.International journal of molecular sciences · 2023Article
- UBE2J1 inhibits colorectal cancer progression by promoting ubiquitination and degradation of RPS3.Oncogene · 2023Article
- Potential biomarkers uncovered by bioinformatics analysis in sotorasib resistant-pancreatic ductal adenocarcinoma.Frontiers in medicine · 2023Article
- Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma.Oncology · 2023Article
- Review
- SIAH1-mediated RPS3 ubiquitination contributes to chemosensitivity in epithelial ovarian cancer.Aging · 2022Article
- Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance.Cancer research · 2022Review
- Article
- RPL17 Promotes Colorectal Cancer Proliferation and Stemness through ERK and NEK2/β-catenin Signaling Pathways.Journal of Cancer · 2022Article
- Deregulation of ribosomal proteins in human cancers.Bioscience reports · 2021Review
- Localization and Functional Roles of Components of the Translation Apparatus in the Eukaryotic Cell Nucleus.Cells · 2021Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radioresistance is considered as a main factor restricting efficacy of radiotherapy. However, the exact molecular mechanism of radioresistance has not been explained yet. In this study, to elucidate radioresistance mechanism in lung cancer, we compared radiation responses in two types of non-small cell lung cancer (NSCLC) cells with different radiosensitivity and identified key molecules conferring radioresistance. In radioresistant NSCLC cells, ionizing radiation (IR) led to casein kinase 2α (CK2α)- and PKC-mediated phosphorylation of rpS3 and TRAF2, respectively, which induced dissociation of rpS3-TRAF2 complex and NF-κB activation, resulting in significant up-regulation of prosurvival genes (cIAP1, cIAP2, and survivin). Also, dissociated phospho-rpS3 translocated into nucleus and bound with NF-κB complex (p65 and p50), contributing to p65 DNA binding property and specificity. However, in radiosensitive NSCLC cells, IR-mediated rpS3 phosphorylation was not detected due to the absence of CK2α overexpression. Consequently, IR-induced rpS3-TRAF2 complex dissociation, NF-κB activation, and prosurvival gene expression were not presented. Taken together, our findings revealed a novel radioresistance mechanism through functional orchestration of rpS3, TRAF2, and NF-κB in NSCLC cells. Moreover, we provided the first evidence for the function of rpS3 as a new TRAF2-binding protein and demonstrated that phosphorylation of both rpS3 and TRAF2 is a key control point of radioresistance in NSCLC cells. These results suggest that regulation of rpS3 and TRAF2 in combination with radiotherapy could have high pharmacological therapeutic potency for radioresistance of NSCLC.
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