ArticleProceedings of the National Academy of Sciences of the United States of America2002
Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- The NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a comprehensive meta-analysis.British journal of cancer · 2013Pooled it
- A functional NQO1 609C>T polymorphism and risk of gastrointestinal cancers: a meta-analysis.PloS one · 2012Pooled it
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pan-cancer molecular signatures connecting aspartate transaminase to cancer prognosis, metabolic and immune signatures.Frontiers in oncology · 2026Article
- Identification of a Ubiquitin-Independent Degron by a Reporter Assay.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Insights into the cellular function and mechanism of action of quinone reductase 2 (NQO2).The Biochemical journal · 2025Review
- Computational modelling identifies primary mediators of crosstalk between DNA damage and oxidative stress responses.PLoS computational biology · 2025Article
- Protein degradation of antizyme depends on the N-terminal degrons.Protein science : a publication of the Protein Society · 2024Article
- Involvement of the oncogenic small nucleolar RNA SNORA24 in regulation of p53 stability in colorectal cancer.Cell biology and toxicology · 2023Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1: Implications of Genetic Diversity of NQO1.Journal of personalized medicine · 2022Review
- Upregulation of wild-type p53 by small molecule-induced elevation of NQO1 in non-small cell lung cancer cells.Acta pharmacologica Sinica · 2022Article
- Utilizing feline oral squamous cell carcinoma patients to develop NQO1-targeted therapy.Neoplasia (New York, N.Y.) · 2021Article
- The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression.International journal of molecular sciences · 2021Review
- Bioactivity Profiles of Cytoprotective Short-Chain Quinones.Molecules (Basel, Switzerland) · 2021Article
- Review
- Article
- Curcumin stabilizes p53 by interaction with NAD(P)H:quinone oxidoreductase 1 in tumor-derived cell lines.Redox biology · 2020Article
- Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.Cancer causes & control : CCC · 2019Article
- Dual-biomarker-triggered fluorescence probes for differentiating cancer cells and revealing synergistic antioxidant effects under oxidative stress.Chemical science · 2019Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor p53 is a labile protein whose level is known to be regulated by the Mdm-2-ubiquitin-proteasome degradation pathway. We have found another pathway for p53 proteasomal degradation regulated by NAD(P)H quinone oxidoreductase 1 (NQO1). Inhibition of NQO1 activity by dicoumarol induces p53 and p73 proteasomal degradation. A mutant p53 (p53([22,23])), which is resistant to Mdm-2-mediated degradation, was susceptible to dicoumarol-induced degradation. This finding indicates that the NQO1-regulated proteasomal p53 degradation is Mdm-2-independent. The tumor suppressor p14(ARF) and the viral oncogenes SV40 LT and adenovirus E1A that are known to stabilize p53 inhibited dicoumarol-induced p53 degradation. Unlike Mdm-2-mediated degradation, the NQO1-regulated p53 degradation pathway was not associated with accumulation of ubiquitin-conjugated p53. In vitro studies indicate that dicoumarol-induced p53 degradation was ubiquitin-independent and ATP-dependent. Inhibition of NQO1 activity in cells with a temperature-sensitive E1 ubiquitin-activating enzyme induced p53 degradation and inhibited apoptosis at the restrictive temperature without ubiquitination. Mdm-2 failed to induce p53 degradation under these conditions. Our results establish a Mdm-2- and ubiquitin-independent mechanism for proteasomal degradation of p53 that is regulated by NQO1. The lack of NQO1 activity that stabilizes a tumor suppressor such as p53 can explain why humans carrying a polymorphic inactive NQO1 are more susceptible to tumor development.
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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.