ArticleJournal of molecular cell biology2018
p53 promotes AKT and SP1-dependent metabolism through the pentose phosphate pathway that inhibits apoptosis in response to Nutlin-3a.
Article in Journal of molecular cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Silencing the long noncoding RNA MALAT1 inhibits vitreous-induced epithelial-mesenchymal transition in RPE cells by regulating the PDGFRs/AKT axis.International ophthalmology · 2024Article
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- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Homo-PROTAC mediated suicide of MDM2 to treat non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2021Article
- P53-regulated autophagy and its impact on drug resistance and cell fate.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Specificity Protein 1: A Protein With a Two-Sided Role in Ischemic Stroke.Frontiers in cellular neuroscience · 2021Review
- Activation of Mitochondrial 2-Oxoglutarate Dehydrogenase by Cocarboxylase in Human Lung Adenocarcinoma Cells A549 Is p53/p21-Dependent and Impairs Cellular Redox State, Mimicking the Cisplatin Action.International journal of molecular sciences · 2020Article
- Taking up the reins of power: metabolic functions of p53.Journal of molecular cell biology · 2019Review
- Inhibition of p53 inhibitors: progress, challenges and perspectives.Journal of molecular cell biology · 2019Review
- p53 modifications: exquisite decorations of the powerful guardian.Journal of molecular cell biology · 2019Review
- The histone demethylase JMJD2B is critical for p53-mediated autophagy and survival in Nutlin-treated cancer cells.The Journal of biological chemistry · 2019Article
- Alpha ketoglutarate levels, regulated by p53 and OGDH, determine autophagy and cell fate/apoptosis in response to Nutlin-3a.Cancer biology & therapy · 2019Article
- Control of metabolism by p53 - Cancer and beyond.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- Advanced Glycation End Products Increase MDM2 Expression via Transcription Factor KLF5.Journal of diabetes research · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Nutlin-3a is a MDM2 antagonist and preclinical drug that activates p53. Cells with MDM2 gene amplification are especially prone to Nutlin-3a-induced apoptosis, though the basis for this is unclear. Glucose metabolism can inhibit apoptosis in response to Nutlin-3a through mechanisms that are incompletely understood. Glucose metabolism through the pentose phosphate pathway (PPP) produces NADPH that can protect cells from potentially lethal reactive oxygen species (ROS). We compared apoptosis and glucose metabolism in cancer cells with and without MDM2 gene amplification treated with Nutlin-3a. Apoptosis in MDM2-amplified cells was associated with a reduction in glycolysis and the PPP, reduced NADPH, increased ROS, and depletion of the transcription factor SP1, which normally promotes PPP gene expression. In contrast, glycolysis and the PPP were maintained or increased in MDM2 non-amplified cells treated with Nutlin-3a. This was dependent on p53-mediated AKT activation and was associated with maintenance of SP1 and continued expression of PPP genes. Knockdown or inhibition of AKT, SP1, or the PPP sensitized MDM2-non-amplified cells to apoptosis. The data indicate that p53 promotes AKT and SP1-dependent activation of the PPP that protects cells from Nutlin-3a-induced apoptosis. These findings provide insight into how glucose metabolism reduces Nutlin-3a-induced apoptosis, and also provide a mechanism for the heightened sensitivity of MDM2-amplified cells to apoptosis in response to Nutlin-3a.
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