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A Role for p53 in the Adaptation to Glutamine Starvation through the Expression of SLC1A3
Open accessAbstract
Numerous mechanisms to support cells under conditions of transient nutrient starvation have been described. Several functions of the tumor-suppressor protein p53 can contribute to the adaptation of cells to metabolic stress and help cancer cell survival under nutrient-limiting conditions. We show here that p53 promotes the expression of SLC1A3, an aspartate/glutamate transporter that allows the utilization of aspartate to support cells in the absence of extracellular glutamine. Under glutamine deprivation, SLC1A3 expression maintains electron transport chain and tricarboxylic acid cycle activity, promoting de novo glutamate, glutamine, and nucleotide synthesis to rescue cell viability. Tumor cells with high levels of SLC1A3 expression are resistant to glutamine starvation, and SLC1A3 depletion retards the growth of these cells in vitro and in vivo, suggesting a therapeutic potential for SLC1A3 inhibition.
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“Recently, SLC1A3, as a crucial effector of p53, has been shown to support cell survival and growth in the absence of glutamine149.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [149]
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Metadata
- Authors
- Tajan, M., Hock, A. K., Blagih, J., Robertson, N. A., Labuschagne, C. F., Kruiswijk, F., Humpton, T. J., Adams, P. D., & Vousden, K. H.
- Affiliations
- The Francis Crick Institute (GB)
- Cancer Research UK Scotland Institute (GB)
- University of Glasgow (GB)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Vousden, Karen H.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 28
- Issue
- 5
- Pages
- 721-736.e6
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6224545
- OpenAlex
- W2885597648
- Cited by
- 230
- References
- 49
- Citations by year
- 2026: 19 · 2025: 21 · 2024: 31 · 2023: 29 · 2022: 40 · 2021: 26 · 2020: 35 · 2019: 24 · 2018: 4
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Wellcome Trust
- Cancer Research UK (C10652/A16566, C596/A10419, C596/A26855, WO/2017/144877)
- Medical Research Council
- Francis Crick Institute
- Astex Pharmaceuticals
- European Research Council (322842-METABOp53)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- p53, GLAST, glutamine starvation, glutamate synthesis, nucleotide synthesis, electron transport chain, TCA cycle, metabolic stress, tumor cell survival, cancer therapy
- MeSH terms
- Adaptation, Physiological, Animals, Cell Survival, Citric Acid Cycle, Female, Glutamine, Humans, Mice, Inbred BALB C, Neoplasms, Starvation, Tumor Suppressor Protein p53, Excitatory Amino Acid Transporter 1, Cell Line, Tumor
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