The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation.

In line with this notion, we found that GCN2 mRNA was upregulated by CB5083, and that this increase in mRNA levels was further accentuated by glutamine depletion, although the changes were numerically small and did not reach statistical significance (Supplementary Figure 9 ).

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While GCN2 depletion did not have a detectable impact on LC3B or p62 levels in most conditions tested, we observed a possible trend to higher LC3BII levels in shGCN2 compared to shNTC cells that were glutamine-depleted, irrespective of whether they were or were not treated with CB5083.

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