Ever-expanding NGLY1 biology.

Abstract

The cytosolic peptide:N-glycanase (PNGase; NGLY1 in humans) is a deglycosylating enzyme that is widely conserved in eukaryotes. This enzyme is involved in the degradation of misfolded N-glycoproteins that are destined for proteasomal degradation in the cytosol, a process that is called endoplasmic reticulum-associated degradation. Although the physiological significance of NGLY1 remained unknown until recently, the discovery of NGLY1 deficiency, a human genetic disorder bearing mutations in the NGLY1 gene, has led to explosive research progress regarding the functional characterization of this enzyme. For example, it is now known that NGLY1 can also act as an 'editing enzyme' to convert N-glycosylated asparagine residues to aspartate residues, thus introducing negative charges into a core peptide and modulating the function of the target molecule. Diverse biological processes have also been found to be affected by compromised NGLY1 activity. In this special issue, recent research progress on the functional characterization of NGLY1 and its orthologues in worm/fly/rodents, assay methods/biomarkers useful for the development of therapeutics and the comprehensive transcriptome/proteome of NGLY1-KO cells as well as patient-derived cells are discussed.

• Authors: Tadashi Suzuki, Yukiko Yoshida
• Journal: Journal of biochemistry (J Biochem) Vol. 171 Issue 2 Pg. 141-143 (Feb 21 2022) ISSN: 1756-2651 [Electronic] England
• PMID: 34969094 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Chemical References

• NGLY1 protein, human
• Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase

Topics

• Biology
• Congenital Disorders of Glycosylation
• Endoplasmic Reticulum-Associated Degradation
• Glycosylation
• Humans
• Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase (chemistry, genetics, metabolism)