Loss of N-Glycanase 1 Alters Transcriptional and Translational Regulation in K562 Cell Lines

Abstract

N-Glycanase 1 (NGLY1) deficiency is an ultra-rare, complex and devastating neuromuscular disease, with multi-organ symptoms. NGLY1 is a deglycosylating protein involved in the degradation of misfolded proteins retrotranslocated from the endoplasmic reticulum (ER). We show that the loss of NGLY1 causes substantial changes in the RNA and protein landscape of K562 cells. We employed the CMap database to predict compounds that can modulate NGLY1 activity. Utilizing our robust K562 screening system, we demonstrate that the compound NVP-BEZ235 promotes degradation of NGLY1-dependent substrates, concurrent with increased autophagic flux, suggesting that autophagy may assist in clearing aberrant substrates during NGLY1 deficiency.