Ever-expanding NGLY1 biology.
Ever-expanding NGLY1 biology.
复制标题
不断扩展的 NGLY1 生物学。
DOI：
10.1093/jb/mvab134
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yukiko Yoshida
中科院分区：
文献类型：
--
作者：
Tadashi Suzuki;Yukiko Yoshida
胞内肽：N-葡聚糖酶(PNGase；在人类中为NGLY1)是一种在真核生物中广泛保守的脱糖基酶。这种酶参与了错误折叠的N-糖蛋白的降解，这些N-糖蛋白注定要在胞浆中被蛋白酶体降解，这一过程被称为内质网相关降解。尽管NGLY1的生理意义直到最近仍不清楚，但NGLY1缺乏症的发现导致了关于该酶功能特征的爆炸性研究进展。NGLY1缺乏症是一种携带NGLY1基因突变的人类遗传病。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，调节靶分子的功能。多种生物学过程也被发现受到NGLY1活性受损的影响。本文就NGLY1及其同源物在虫、蝇、啮齿动物体内的功能特征、可用于治疗的检测方法/生物标志物以及NGLY1-KO细胞和患者来源细胞的综合转录组/蛋白质组的最新研究进展进行了综述。
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 misfoldedN-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 theNGLY1gene, 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 convertN-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 ofNGLY1-KO cells as well as patient-derived cells are discussed.