p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake
Summary: 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 metabol...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719302086 |
| _version_ | 1818063940764041216 |
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| author | Xazmin H. Lowman Eric A. Hanse Ying Yang Mari B. Ishak Gabra Thai Q. Tran Haiqing Li Mei Kong |
| author_facet | Xazmin H. Lowman Eric A. Hanse Ying Yang Mari B. Ishak Gabra Thai Q. Tran Haiqing Li Mei Kong |
| author_sort | Xazmin H. Lowman |
| collection | DOAJ |
| description | Summary: 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. : Lowman et al. show that glutamine deprivation induces Slc7a3 to increase intracellular arginine levels in a p53-dependent manner. This induction transiently sustains mTORC1 activity and contributes to cellular adaptation to low glutamine conditions. Keywords: p53 activation, Slc7a3, glutamine deprivation, arginine |
| first_indexed | 2024-12-10T14:28:05Z |
| format | Article |
| id | doaj.art-436fe2b531ba49b3a816c5598a9e6dd7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T14:28:05Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-436fe2b531ba49b3a816c5598a9e6dd72022-12-22T01:45:00ZengElsevierCell Reports2211-12472019-03-01261130513060.e4p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine UptakeXazmin H. Lowman0Eric A. Hanse1Ying Yang2Mari B. Ishak Gabra3Thai Q. Tran4Haiqing Li5Mei Kong6Department of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USADepartment of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USADepartment of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USADepartment of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USADepartment of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USACenter 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, USADepartment of Molecular Biology and Biochemistry; University of California, Irvine, Irvine, CA 92697, USA; Corresponding authorSummary: 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. : Lowman et al. show that glutamine deprivation induces Slc7a3 to increase intracellular arginine levels in a p53-dependent manner. This induction transiently sustains mTORC1 activity and contributes to cellular adaptation to low glutamine conditions. Keywords: p53 activation, Slc7a3, glutamine deprivation, argininehttp://www.sciencedirect.com/science/article/pii/S2211124719302086 |
| spellingShingle | Xazmin H. Lowman Eric A. Hanse Ying Yang Mari B. Ishak Gabra Thai Q. Tran Haiqing Li Mei Kong p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake Cell Reports |
| title | p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake |
| title_full | p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake |
| title_fullStr | p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake |
| title_full_unstemmed | p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake |
| title_short | p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake |
| title_sort | p53 promotes cancer cell adaptation to glutamine deprivation by upregulating slc7a3 to increase arginine uptake |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719302086 |
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