ERO1 alpha deficiency impairs angiogenesis by increasing N-glycosylation of a proangiogenic VEGFA.

ABSTRACT: 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-t

SUBMITTER: Varone E 

PROVIDER: S-EPMC9463388 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature