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Literature summary for 3.5.1.1 extracted from

  • Bunpo, P.; Cundiff, J.K.; Reinert, R.B.; Wek, R.C.; Aldrich, C.J.; Anthony, T.G.
    The eIF2 kinase GCN2 is essential for the murine immune system to adapt to amino acid deprivation by asparaginase (2010), J. Nutr., 140, 2020-2027.
    View publication on PubMedView publication on EuropePMC
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Organism

Organism UniProt Comment Textmining
Mus musculus
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Source Tissue

Source Tissue Comment Organism Textmining

General Information

General Information Comment Organism
physiological function amino acid starvation by asparaginase enhances phosphorylation of eukaryotic initiation factor 2, eIF2 by general control nonderepressible 2 kinase GCN2, leading to reduced global mRNA translation rates. GCN2+/+ and GCN2-/-2 mice are injected once daily with asparaginase or saline for up to 7 d. In both thymus and spleen, activation of amino acid stress response genes to asparaginase, such as asparagine synthetase and CAAT enhancer binding protein homologous protein, requires GCN2. Asparaginase reduces food intake and body weight in both genotypes, but spleen and thymus wet weights and total cell numbers in thymus, spleen, bone marrow, and mesenteric lymph nodes are less in GCN2-/- mice treated with asparaginase. In the thymus, GCN2-/- mice treated with asparaginase demonstrate enhanced apoptosis and fewer cells in all subpopulations examined compared with GCN2+/+ mice treated with asparaginase. In the spleen, GCN2 deletion magnifies asparaginase-induced reductions in CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD11b+ leukocytes Mus musculus