Figure 4.

Schematic representation showing that under normal conditions, retrotranslocation from ER to cytosol directs NFE2L1 to its proteasomal degradation. Upon proteasomal inhibition, NFE2L1 undergoes de-N-glycosylation by NGLY1 and is cleaved by an aspartic protease called DNA damage-inducible 1 homolog 2 (DDI2), which leads to its activation. Activated NFE2L1 enters the nucleus and induces the transcription of proteasomal subunit genes, as well as its other target genes. N, asparagine; D, aspartic acid.