Glycometabolome Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama 351-0198, Japan.
Takeda-CiRA Joint Program (T-CiRA), Kanagawa 251-8555, Japan.
J Biochem. 2022 Feb 21;171(2):141-143. doi: 10.1093/jb/mvab134.
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.
N-糖基酶（PNGase；人类中的 NGLY1）是一种广泛存在于真核生物中的糖基水解酶。该酶参与降解错误折叠的 N-糖蛋白，这些糖蛋白注定要在细胞质中被蛋白酶体降解，这一过程被称为内质网相关降解。尽管直到最近，NGLY1 的生理意义仍不清楚，但 NGLY1 缺乏症（一种携带 NGLY1 基因突变的人类遗传疾病）的发现，导致了对该酶功能特征的研究取得了突破性进展。例如，现在已知 NGLY1 还可以作为一种“编辑酶”，将 N-糖基化的天冬酰胺残基转化为天冬氨酸残基，从而在核心肽中引入负电荷，并调节靶分子的功能。还发现多种生物学过程受到 NGLY1 活性受损的影响。在本期特刊中，讨论了 NGLY1 及其在蠕虫/蝇/啮齿动物中的同源物的功能特征的最新研究进展、用于开发治疗方法的测定方法/生物标志物、NGLY1-KO 细胞以及患者来源细胞的综合转录组/蛋白质组。
