30122553.pdf (3.7 MB)
A role for p53 in the adaptation to glutamine starvation through the expression of SLC1A3
journal contributionposted on 2020-09-14, 10:28 authored by Mylène Tajan, Andreas K Hock, Julianna Blagih, Neil A Robertson, Christiaan F Labuschagne, Flore Kruiswijk, Timothy J Humpton, Peter D Adams, Karen H Vousden
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.
SLC1A3aspartate metabolismglutamine starvationp53Adaptation, PhysiologicalAnimalsCell Line, TumorCell SurvivalCitric Acid CycleExcitatory Amino Acid Transporter 1FemaleGlutamineHumansMice, Inbred BALB CNeoplasmsStarvationTumor Suppressor Protein p53Vousden FC001557MET-ackBRF-ack0601 Biochemistry and Cell Biology1101 Medical Biochemistry and MetabolomicsEndocrinology & Metabolism