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Cell Rep. 2019 Mar 12;26(11):3051-3060.e4. doi: 10.1016/j.celrep.2019.02.037.

p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake.

Author information

1
Department of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USA.
2
Center for Informatics, City of Hope National Medical Center, Duarte, CA 91010, USA; Department of Computational & Quantitative Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
3
Department of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USA. Electronic address: meik1@uci.edu.

Abstract

Cancer cells heavily depend on the amino acid glutamine to meet the demands associated with growth and proliferation. Due to the rapid consumption of glutamine, cancer cells frequently undergo glutamine starvation in vivo. We and others have shown that p53 is a critical regulator in metabolic stress resistance. To better understand the molecular mechanisms by which p53 activation promotes cancer cell adaptation to glutamine deprivation, we identified p53-dependent genes that are induced upon glutamine deprivation by using RNA-seq analysis. We show that Slc7a3, an arginine transporter, is significantly induced by p53. We also show that increased intracellular arginine levels following glutamine deprivation are dependent on p53. The influx of arginine has minimal effects on known metabolic pathways upon glutamine deprivation. Instead, we found arginine serves as an effector for mTORC1 activation to promote cell growth in response to glutamine starvation. Therefore, we identify a p53-inducible gene that contributes to the metabolic stress response.

KEYWORDS:

Slc7a3; arginine; glutamine deprivation; p53 activation

PMID:
30865893
DOI:
10.1016/j.celrep.2019.02.037
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