Anti-NGLY1 (aa 100-200) polyclonal antibody

Peptide:N-glycanase (PNGase) is a deglycosylating enzyme that acts on asparagine-linked (N-linked) glycans. I was involved in the discovery of this enzyme activity in 1993, as well as the identification of the gene encoding this enzyme in 2000. In 2007, I proposed the existence of a novel "non-lysosomal" glycan degradation pathway in which cytoplasmic PNGase plays pivotal roles. In 2008, I was fortunate to receive a Young Investigator Award from the Japanese Society of Carbohydrate Research. Since that time remarkable progress has been made regarding the functional analysis of the cytoplasmic PNGase (NGLY1 in mammals). After the discovery of a human genetic disorder, an NGLY1-deficiency, caused by the genetic mutations of NGLY1 gene, the functional importance of this enzyme has attracted widespread interest. In this article, I briefly summarize recent research progress on NGLY1.

N-Glycosylated substrates that undergo ER-associated degradation (ERAD) are often deglycosylated by the cytosolic peptide:N-glycanase (Ngly1) during their proteasomal degradation in the cytosol. Consequently, the presence of non- or deglycosylated forms of such proteins after treatment with proteasome inhibitors is widely used as evidence for cytosolic deglycosylation by Ngly1. However, in this study, the accumulation of nonglycosylated RTA increment m, a model ERAD substrate, was still observed in mouse cells lacking cytosolic de-N-glycosylating enzymes, when treated with proteasome inhibitors. It was found that RTA increment m is normally partially N-glycosylated, while the nonglycosylated form is rapidly degraded by proteasomes in the cytosol. Our results suggest that the occurrence of 'nonglycosylated' ERAD substrates upon treatment with proteasome inhibitors is not necessarily a clue for cytosolic deglycosylation.