ArticleScientific reports2019
Metabolic stress controls mutant p53 R248Q stability in acute myeloid leukemia cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.Cellular & molecular biology letters · 2026Review
- Autophagy and Lipid Metabolism as a Therapeutic Target for Overcoming Drug Resistance in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2026Review
- Mutational Disruption of TP53: A Structural Approach to Understanding Chemoresistance.International journal of molecular sciences · 2025Article
- Dichloroacetate enhances Chemo-sensitivity in wild-type P53 breast cancer cells by modulating ABCG2 and NKG2DL.Scientific reports · 2025Article
- Current Understanding of the Role of Autophagy in the Treatment of Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Bioinformatic Characterization of the Functional and Structural Effect of Single Nucleotide Mutations in Patients with High-Grade Glioma.Biomedicines · 2024Article
- Review
- Article
- Regulated cell death (RCD) in cancer: key pathways and targeted therapies.Signal transduction and targeted therapy · 2022Review
- The dual role of autophagy in acute myeloid leukemia.Journal of hematology & oncology · 2022Review
- The metabolism of cells regulates their sensitivity to NK cells depending on p53 status.Scientific reports · 2022Article
- Metformin sensitizes leukemic cells to cytotoxic lymphocytes by increasing expression of intercellular adhesion molecule-1 (ICAM-1).Scientific reports · 2022Article
- Review
- Autophagy a Close Relative of AML Biology.Biology · 2021Review
- From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy.International journal of molecular sciences · 2021Review
- Article
- Pros and Cons of Chaperone-Mediated Autophagy in Cancer Biology.Trends in endocrinology and metabolism: TEM · 2020Review
- Mutant p53 as a Regulator and Target of Autophagy.Frontiers in oncology · 2020Review
- Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eliminating mutant p53 (mt p53) protein could be a useful strategy to treat mt p53 tumors and potentially improve the prognosis of cancer patients. In this study, we unveil different mechanisms that eliminate p53-R248Q, one of the most frequent mutants found in human cancers. We show that the Hsp90 inhibitor 17-AAG eliminates R248Q by stimulating macroautophagy under normal growth conditions. Metabolic stress induced by the pyruvate dehydrogenase kinase-1 (PDK1) inhibitor dichloroacetate (DCA) inhibits the macroautophagy pathway. This induces the accumulation of R248Q, which in addition further inhibits macroautophagy. Combination of DCA and 17-AAG further decreases the autophagy flux compared to DCA alone. Despite this, this co-treatment strongly decreases R248Q levels. In this situation of metabolic stress, 17-AAG induces the binding of p53-R248Q to Hsc70 and the activation of Chaperone-Mediated Autophagy (CMA), leading to higher R248Q degradation than in non-stress conditions. Thus, different metabolic contexts induce diverse autophagy mechanisms that degrade p53-R248Q, and under metabolic stress, its degradation is CMA-mediated. Hence, we present different strategies to eliminate this mutant and provide new evidence of the crosstalk between macroautophagy and CMA and their potential use to target mutant p53.
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