Oligosaccharyltransferase: A Gatekeeper of Health and Tumor Progression

Abstract

Oligosaccharyltransferase (OST) is a multi-span membrane protein complex that catalyzes the addition of glycans to selected Asn residues within nascent polypeptides in the lumen of the endoplasmic reticulum. This process, termed N-glycosylation, is a fundamental post-translational protein modification that is involved in the quality control, trafficking of proteins, signal transduction, and cell-to-cell communication. Given these crucial roles, N-glycosylation is essential for homeostasis at the systemic and cellular levels, and a deficiency in genes that encode for OST subunits often results in the development of complex genetic disorders. A growing body of evidence has also demonstrated that the expression of OST subunits is cell context-dependent and is frequently altered in malignant cells, thus contributing to tumor cell survival and proliferation. Importantly, a recently developed inhibitor of OST has revealed this enzyme as a potential target for the treatment of incurable drug-resistant tumors. This review summarizes our current knowledge regarding the functions of OST in the light of health and tumor progression, and discusses perspectives on the clinical relevance of inhibiting OST as a tumor treatment.

Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas

“…In addition to being correlated with abundance changes of TRY1 and PNPH, the increase in SSRG was associated with the increase in RPN1 (dolichyl-diphosphooligosaccharide-protein glycosyltransferase) and HS71B (heat shock cognate 70-kDa protein 1B, encoded by HSPA1B gene in human). RPN1 is involved in the N-glycosylation of proteins, whose dysregulation in cancers began to be deciphered at the molecular level during the last decade [ 57 ], with interesting prospects for innovative therapies [ 58 ]. Elevated levels of HS71B (also named Hsp 70-2) in cancer cells may be responsible for tumorigenesis and for tumor progression by providing resistance to chemotherapy.…”

ARL15 modulates magnesium homeostasis through N-glycosylation of CNNMs

“…1). RPN1 is part of the oligosaccharyltransferase complex that is involved in N-glycosylation and is found in the ER [19]. To confirm the interaction, coimmunoprecipitation assays with overexpressed CNNM3, ARL15 and RPN1 were performed (Supp.…”

The Crucial Role of Demannosylating Asparagine-Linked Glycans in ERADicating Misfolded Glycoproteins in the Endoplasmic Reticulum

“…N -glycosylation is initiated by a single-step en bloc transfer of a preassembled Glc 3 Man 9 GlcNAc 2 from its lipid carrier dolichyl pyrophosphate (Dol-PP) to select asparagine (Asn or N) residues within the Asn-X-Ser/Thr sequon (X indicating any amino acid except proline while Ser/Thr denoting serine/threonine residue) of a nascent polypeptide. This transfer reaction is catalyzed by a multisubunit enzyme complex known as oligosaccharide transferase (OST) ( Strasser, 2016 ; Harada et al, 2019 ) ( Figure 1 ). The assembly of the three-branched Dol-PP-Glc 3 Man 9 GlcNAc 2 is a highly conserved pathway involving two topologically distinct sets of glycosyltransfer reactions on both sides of the ER membrane catalyzed sequentially by highly specific glycosyltransferases ( Figure 1 ) ( Schachter, 2014 ; Stanley et al, 2015 ).…”