A Role for p53 in the Adaptation to Glutamine Starvation through the Expression of SLC1A3
CELL METABOLISM
Authors: Tajan, Mylene; Hock, Andreas K.; Blagih, Julianna; Robertson, Neil A.; Labuschagne, Christiaan F.; Kruiswijk, Flore; Humpton, Timothy J.; Adams, Peter D.; Vousden, Karen H.
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.
Glutamate and glutamine transporter genes in grass carp (Ctenopharyngodon idellus): Molecular cloning, characterization and expression in response to different stocking densities
AQUACULTURE RESEARCH
Authors: Liang, Xiao; Fang, Tongzhu; Yan, Fengying; Xu, Weitong; Onxayvieng, Kommaly; Tang, Rong; Li, Li; Zhang, Xi; Chi, Wei; Li, Dapeng
Abstract
Active transporters play a central role in the uptake and efflux of glutamate by cells and organelles. We aimed to assess the effects of crowding stress on the efficiency of active glutamate and glutamine transport in fish. We cloned intestinal-related transporters and investigated their transcriptional changes in grass carpCtenopharyngodon idellusexposed to different stocking densities. The full-length cDNA sequences ofslc1a1,slc1a3andslc7a6cloned by rapid amplification of cDNA ends were 2,869, 2,508 and 2,141 base pairs respectively. Based on homology modelling, we derived three-dimensional models of SLC1A1, SLC1A3, SLC7A6 and SLC7A7 and noted their transmembrane domains. The expression profiles ofslc1a1,slc1a3andslc7a7demonstrated tissue specificity, with section-dependent expression patterns along the intestine. Moreover, segmental mRNA expression patterns ofslc1a3,slc7a6andslc7a7were affected by stocking density. Crowding stress notably altered the segment-specific mRNA expression ofslc7a6. The results of this study showed that increased stocking density increased mRNA expression levels of glutamine transporters (slc7a6andslc7a7) but decreased mRNA expression of the glutamate transporter (slc1a3). These results furthered our understanding of the relationship between crowding stress and intestinal glutamate/glutamine transport in fish.