Details

Autor(en) / Beteiligte

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

Titel

A Role for p53 in the Adaptation to Glutamine Starvation through the Expression of SLC1A3

Ist Teil von

• Cell metabolism, 2018-11, Vol.28 (5), p.721-736.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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. [Display omitted] •p53 promotes cancer cell proliferation and survival under glutamine starvation•Aspartate metabolism supported by SLC1A3 is important under glutamine deprivation•SLC1A3 expression is induced by p53•Depletion of SLC1A3 impairs tumor growth in vivo Tajan et al. show that the ability of cells to survive glutamine depletion depends on aspartate metabolism, which is supported by the aspartate/glutamate transporter SLC1A3. The tumor suppressor p53 induces SLC1A3 expression. Tumor cells with high SLC1A3 expression are resistant to glutamine starvation, and SLC1A3 depletion retards cell growth.