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Regulation of autophagy by cytoplasmic p53
Open accessAbstract
Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53(-/-) cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53.
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“Autophagy is another cellular program that is triggered by cell stress and p53.195, 208”
From Census and evaluation of p53 target genes (2017) · cites this paper as [208]
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Metadata
- Authors
- Tasdemir, E., Maiuri, M. C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., Nannmark, U., Samara, C., Pinton, P., Vicencio, J. M., Carnuccio, R., Moll, U. M., Madeo, F., Paterlini-Brechot, P., Rizzuto, R., Szabadkai, G., Pierron, G., Blomgren, K., Tavernarakis, N., Codogno, P., Cecconi, F., & Kroemer, G.
- Affiliations
- Université Paris-Sud (FR)
- Inserm (FR)
- Drottning Silvias barn- och ungdomssjukhus (SE)
- Centre National de la Recherche Scientifique (FR)
- University of Gothenburg (SE)
- Foundation for Research and Technology Hellas (GR)
- University of Ferrara (IT)
- University of Naples Federico II (IT)
- Stony Brook University (US)
- University of Graz (AT)
- University of Rome Tor Vergata (IT)
- Corresponding author
- Kroemer, Guido
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2008-05-04
- Volume
- 10
- Issue
- 6
- Pages
- 676-687
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC2676564
- OpenAlex
- W2157699677
- Cited by
- 1,132
- References
- 50
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 40 · 2023: 44 · 2022: 48 · 2021: 62 · 2020: 65 · 2019: 58 · 2018: 68 · 2017: 58 · 2016: 68 · 2015: 57 · 2014: 74 · 2013: 96 · 2012: 91
- FWCI
- 61.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institute on Aging (P01AG025532)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- autophagy, cytoplasmic p53, p53 degradation, MDM2, E3 ubiquitin ligase, proteasomal degradation, hypoxia, nutrient depletion, ATP maintenance, enucleated cells, starvation, rapamycin, endoplasmic reticulum stress, tumour suppressor
- MeSH terms
- Animals, Hypoxia, Autophagy, Cytoplasm, Endoplasmic Reticulum, Gene Expression Regulation, Humans, Lysosomes, Mice, Transgenic, Models, Biological, Genes, p53, Tumor Suppressor Protein p53, Cell Line, Tumor, Proteasome Endopeptidase Complex, Mice
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