ArticleThe Journal of biological chemistry2012
Nuclear EGFR suppresses ribonuclease activity of polynucleotide phosphorylase through DNAPK-mediated phosphorylation at serine 776.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Sortilin exhibits tumor suppressor-like activity by limiting EGFR transduction function.Oncogene · 2026Article
- Human polynucleotide phosphorylase in mitochondrial RNA metabolism.Bioscience reports · 2025Review
- BRAFbioRxiv : the preprint server for biology · 2025Article
- ARF4-mediated retrograde trafficking as a driver of chemoresistance in glioblastoma.Neuro-oncology · 2024Article
- Proteomic characterization and cytotoxic potential of proteins from Cuscuta (Cuscuta epithymum (L.) crude herbal product against MCF-7 human breast cancer cell line.BMC complementary medicine and therapies · 2024Article
- Proscillaridin A inhibits lung cancer cell growth and motility through downregulation of the EGFR-Src-associated pathway.American journal of cancer research · 2023Article
- SP1 and NFY Regulate the Expression ofInternational journal of molecular sciences · 2022Article
- Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase.International journal of molecular sciences · 2022Review
- Retracted Article: Down-regulation of the radiation-induced pEGFRRSC advances · 2020Article
- CGRRF1, a growth suppressor, regulates EGFR ubiquitination in breast cancer.Breast cancer research : BCR · 2019Article
- PNPase knockout results in mtDNA loss and an altered metabolic gene expression program.PloS one · 2018Article
- Twist1 Enhances Hypoxia Induced Radioresistance in Cervical Cancer Cells by Promoting Nuclear EGFR Localization.Journal of Cancer · 2017Article
- New roles for nuclear EGFR in regulating the stability and translation of mRNAs associated with VEGF signaling.PloS one · 2017Article
- Mitochondrial BMI1 maintains bioenergetic homeostasis in cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- NF-κB-driven suppression of FOXO3a contributes to EGFR mutation-independent gefitinib resistance.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Regulation of therapeutic resistance in cancers by receptor tyrosine kinases.American journal of cancer research · 2016Article
- EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug scheduling and patient selection.Pharmacology & therapeutics · 2015Review
- Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response.Cell research · 2015Article
- Non-canonical signaling mode of the epidermal growth factor receptor family.American journal of cancer research · 2015Review
- EGFR modulates DNA synthesis and repair through Tyr phosphorylation of histone H4.Developmental cell · 2014Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Nuclear existence of epidermal growth factor receptor (EGFR) has been documented for more than two decades. Resistance of cancer to radiotherapy is frequently correlated with elevated EGFR expression, activity, and nuclear translocation. However, the role of nuclear EGFR (nEGFR) in radioresistance of cancers remains elusive. In the current study, we identified a novel nEGFR-associated protein, polynucleotide phosphorylase (PNPase), which possesses 3' to 5' exoribonuclease activity toward c-MYC mRNA. Knockdown of PNPase increased radioresistance. Inactivation or knock-down of EGFR enhanced PNPase-mediated c-MYC mRNA degradation in breast cancer cells, and also increased its radiosensitivity. Interestingly, the association of nEGFR with PNPase and DNA-dependent protein kinase (DNAPK) increased significantly in breast cancer cells after exposure to ionizing radiation (IR). We also demonstrated that DNAPK phosphorylates PNPase at Ser-776, which is critical for its ribonuclease activity. The phospho-mimetic S776D mutant of PNPase impaired its ribonuclease activity whereas the nonphosphorylatable S776A mutant effectively degraded c-MYC mRNA. Here, we uncovered a novel role of nEGFR in radioresistance, and that is, upon ionizing radiation, nEGFR inactivates the ribonuclease activity of PNPase toward c-MYC mRNA through DNAPK-mediated Ser-776 phosphorylation, leading to increase of c-MYC mRNA, which contributes to radioresistance of cancer cells.
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Registered trials
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.