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Consistent with the findings from yeast in the current work, our previous characterizations of FL-associated V-ATPase mutants in human cells also found that when an FL-associated V-ATPase mutant is expressed, ATF4/Gcn4 is strongly induced 18 , suggesting that the V-ATPase-dependent autophagy pathway shares conserved regulatory mechanisms in eukaryotes

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This proline-rich sequence introduces conformational rigidity that strongly resists proteolytic degradation by trypsin, chymotrypsin, and catheptic proteases