ArticleProceedings of the National Academy of Sciences of the United States of America2008
p53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 148 citations in OpenAlex.
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- Liprin-α1 enhances PHLDB3 oncogenic function in colorectal cancer via activation of mTORC2-AKT1 pathway.Cell reports · 2026Article
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- Targeting legumain-mediated cell-cell interaction sensitizes glioblastoma to immunotherapy in preclinical models.The Journal of clinical investigation · 2025Article
- Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage.Cell death discovery · 2025Article
- A comprehensive review of sensors of radiation-induced damage, radiation-induced proximal events, and cell death.Immunological reviews · 2025Review
- KNO1-mediated autophagic degradation of the Bloom syndrome complex component RMI1 promotes homologous recombination.The EMBO journal · 2023Article
- Distinct p53 phosphorylation patterns in chronic lymphocytic leukemia patients are reflected in the activation of circumjacent pathways upon DNA damage.Molecular oncology · 2023Article
- Synergistic cytotoxicity of fludarabine, clofarabine, busulfan, vorinostat and olaparib in AML cells.Frontiers in oncology · 2023Article
- Deciphering the Role and Signaling Pathways of PKCα in Luminal A Breast Cancer Cells.International journal of molecular sciences · 2022Article
- A p53-phosphoinositide signalosome regulates nuclear AKT activation.Nature cell biology · 2022Article
- Article
- DNA-PK promotes activation of the survival kinase AKT in response to DNA damage through an mTORC2-ECT2 pathway.Science signaling · 2022Article
- MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response.Frontiers in pharmacology · 2022Review
- When PIPFrontiers in cell and developmental biology · 2022Review
- Article
- Regulation of p53 by E3s.Cancers · 2021Review
- Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways.Nature communications · 2020Article
- DNA-PKcs: A Multi-Faceted Player in DNA Damage Response.Frontiers in genetics · 2020Review
- Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 protein is one of the major tumor suppressor proteins. In response to DNA damage, p53 is prevented from degradation and accumulates to high levels. Ionizing radiation leads to hypophosphorylation of the p53 ubiquitin ligase Mdm2 at sites where phosphorylation is critical for p53 degradation and to the phosphorylation and activation of Akt/PKB, a kinase that phosphorylates and inhibits GSK-3. GSK-3, which normally phosphorylates Mdm2, is inactivated in response to ionizing radiation. We show that p53 accumulates in lymphoblasts from patients with the hereditary disorder ataxia telangiectasia in response to ionizing radiation despite the absence of a functional ATM kinase. Also, knockdown of ATR did not prevent p53 accumulation in response to ionizing radiation. Instead, p53 stabilization in response to ionizing radiation depended on the inactivation of GSK-3 and the presence of Akt/PKB. Akt/PKB is a target of DNA-PK, a kinase that is activated after ionizing radiation. Correspondingly, down-regulation of DNA-PK prevented phosphorylation of Akt/PKB and GSK-3 after ionizing radiation and strongly reduced the accumulation of p53. We therefore propose a signaling cascade for the regulation of p53 in response to ionizing radiation that involves activation of DNA-PK and Akt/PKB and inactivation of GSK-3 and Mdm2.
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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.