糖基化
血管生成
化学
N-连接糖基化
内质网
细胞生物学
串扰
生物化学
调节器
糖蛋白
生物
癌症研究
聚糖
物理
光学
基因
作者
Ersilia Varone,Alexander Chernorudskiy,Alessandro Cherubini,Angela Cattaneo,Ángela Bachi,Stefano Fumagalli,Gizem Erol,Marco Gobbi,Michael J. Lenardo,Nica Borgese,Ester Zito
出处
期刊:Redox biology
[Elsevier]
日期:2022-10-01
卷期号:56: 102455-102455
被引量:6
标识
DOI:10.1016/j.redox.2022.102455
摘要
N-glycosylation and disulfide bond formation are two essential steps in protein folding that occur in the endoplasmic reticulum (ER) and reciprocally influence each other. Here, to analyze crosstalk between N-glycosylation and oxidation, we investigated how the protein disulfide oxidase ERO1-alpha affects glycosylation of the angiogenic VEGF121, a key regulator of vascular homeostasis. ERO1 deficiency, while retarding disulfide bond formation in VEGF121, increased utilization of its single N-glycosylation sequon, which lies close to an intra-polypeptide disulfide bridge, and concomitantly slowed its secretion. Unbiased mass-spectrometric analysis revealed interactions between VEGF121 and N-glycosylation pathway proteins in ERO1-knockout (KO), but not wild-type cells. Notably, MAGT1, a thioredoxin-containing component of the post-translational oligosaccharyltransferase complex, was a major hit exclusive to ERO1-deficient cells. Thus, both a reduced rate of formation of disulfide bridges, and the increased trapping potential of MAGT1 may increase N-glycosylation of VEGF121. Extending our investigation to tissues, we observed altered lectin staining of ERO1 KO breast tumor xenografts, implicating ERO1 as a physiologic regulator of protein N-glycosylation. Our study, highlighting the effect of ERO1 loss on N-glycosylation of proteins, is particularly relevant not only to angiogenesis but also to other cancer patho-mechanisms in light of recent findings suggesting a close causal link between alterations in protein glycosylation and cancer development.
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