Figure 7.

Proposed model of cell fate decisions following asparagine depletion. Asparagine depletion induces ATF4 through a GCN2-dependent amino acid response. When the ASNS promoter is hypomethylated, ATF4 is recruited to the promoter region to induce gene expression. As a result, increased expression of ASNS drives de novo biosynthesis of asparagine to support cell survival and growth (left). When the ASNS promoter is hypermethylated, ATF4 recruitment is blocked. Consequently, failure to induce ASNS expression leads to intracellular deficiency, which triggers CHOP induction and apoptosis in an ATF4-independent manner (right).