A role for p53 in the adaptation to glutamine starvation through the expression of SLC1A3

Mylène Tajan, Andreas K. Hock, Julianna Blagih, Neil A. Robertson, Christiaan F. Labuschagne, Flore Kruiswijk, Timothy J. Humpton, Peter D. Adams, Karen H. Vousden*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Citations (Scopus)
2 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)721-736. E6
Number of pages23
JournalCell Metabolism
Volume28
Issue number5
Early online date16 Aug 2018
DOIs
Publication statusPublished - 6 Nov 2018
Externally publishedYes

Keywords

  • aspartate metabolism
  • glutamine starvation
  • p53
  • SLC1A3

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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