Ask about this productRelated genes to: UGCGL1 antibody
- Gene:
- UGGT1 NIH gene
- Name:
- UDP-glucose glycoprotein glucosyltransferase 1
- Previous symbol:
- UGCGL1
- Synonyms:
- HUGT1
- Chromosome:
- 2q14.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-05
- Date modifiied:
- 2014-11-19
Related products to: UGCGL1 antibody
Related articles to: UGCGL1 antibody
- Human N-glycoproteins represent a market worth hundreds of billions of dollars, yet their production in yeast is often limited by misfolding and degradation. However, few strategies have addressed this limitation by targeting differences between human and yeast N-glycan-dependent protein quality control (QC), including the absence of the UGGT-mediated reglucosylation-refolding cycle and the simpler glycoprotein degradation pathway in yeast. Here, we engineered the glycoprotein QC system of Kluyveromyces marxianus by introducing key human components and modifying native pathways. Human UGGT1 or UGGT2 enhanced soluble and secretory glycoprotein production in an activity-dependent manner, with further improvements achieved by co-expressing the human cochaperone SEP15 and reducing native glucosidase II trimming. Human EDEM2 delayed endoplasmic reticulum-associated degradation and increased secretion. Combining these strategies enhanced the production of diverse N-glycoproteins, including Fc, γ-glutamyl hydrolase, fungal xylanase, and Fc-fusion therapeutics, by up to ∼12-fold, demonstrating an effective strategy for engineering human-like glycoprotein QC in yeast to improve glycoprotein production. - Source: PubMed
Publication date: 2026/07/31
Ai YiHe YutingZhao LunqiangLi MiaomiaoWang YongmingZhou JungangLu HongYu Yao - Fluorescently labeled glycans are widely used as chemical probes to study glycoprotein processing and quality control; however, they are generally regarded as passive reporters of enzymatic activity. In contrast, the development of glycan probe that can actively control enzymatic activity remains an important challenge in chemical biology. Herein, we report a switchable glycan probe that actively modulates UDP-glucose: glycoprotein glucosyltransferase 1 (UGGT1) activity through a pH-responsive aglycone design. A ManGlcNAc-Asn conjugate bearing fluorescein was synthesized, in which the fluorescein aglycone undergoes reversible pH-dependent structural interconversion, altering its physicochemical character. UGGT1 assays revealed that the switchable glycan probe exhibits glucose transfer activity in the order of pH 6.0 > pH 8.5, while a unresponsive control probe showed no pH-dependent change in activity. Furthermore, UGGT1 activity could be dynamically switched during the reaction by changing the pH. These results demonstrate that aglycone structural populations can actively regulate UGGT1 activity, providing the first example of controlling UGGT1-mediated glucose transfer using a single, environmentally switchable glycan probe. This work establishes an innovative molecular design strategy, opening a conceptual framework to probe and manipulate ER glycoprotein quality control mechanism using chemically programmable glycan probes. - Source: PubMed
Publication date: 2026/08/04
Hirose MitsuakiSuzuki YukaMiyuki RentaroOki KosukeSato KeirinYokoyama AkihiroTotani Kiichiro - Chinese hamster ovary (CHO) cells are widely utilised in the biopharmaceutical industry to produce therapeutic proteins. Understanding the mechanisms of endoplasmic reticulum (ER) stress and its interplay with protein degradation pathways remains pivotal for improving production efficiency and product quality. In this study, we investigated the proteomic responses of CHO-K1 (non-producer), CHO DP-12 (IgG-producer), and NISTCHO (IgG-producer) cell lines under ER stress induced by a combination of the proteasome inhibitor MG132 and the glycosylation inhibitor tunicamycin. Viability, cell growth, and IgG titre were measured after 24 h, 48 h, and 72 h of treatment and the 48 h timepoint was used for the comparative analysis of the proteomic data across the three cell lines. Proteasome inhibition with MG132 intensified ER stress and altered ER-associated protein degradation (ERAD). Combined tunicamycin + MG132 treatment was associated with cell line-specific proteomic changes: NISTCHO upregulated ER translocation and glycoprotein quality control proteins (SSR4, SEC24C, UGGT1), CHO DP-12 activated redox/disulfide regulators (DNAJC10, CAPN1), while CHO-K1 showed broad proteome shifts, suggesting differences in baseline stress handling. These findings provide mechanistic insights into ER stress and protein quality control in CHO cells, offering a foundation for strategies to enhance cell line robustness and optimise biopharmaceutical production. - Source: PubMed
Publication date: 2026/02/10
Sideri Christiana-KondyloRyan DavidHenry MichaelEfeoglu EsenMeleady Paula - Most nascent glycoproteins entering the endoplasmic reticulum (ER) undergo quality control via the calnexin/calreticulin (CNX/CRT) cycle, wherein GlcManGlcNAc (G1M9)-type glycans play a crucial role in monitoring protein folding. We have recently identified an endo-α-mannosidase activity within the ER, designated as ER-EM, which facilitates the release of misfolded glycoproteins from this cycle by converting G1M9-proteins into ManGlcNAc (M8A)-proteins in a single step. ER-EM appears to function as a complex comprising UDP-Glc:glycoprotein glucosyltransferase 1 (UGGT1), ERp57, and carboxylesterase 1D (Ces1d), although the role of Ces1d-primarily recognized for its involvement in lipid metabolism-in glycan-associated substrate recognition remains unclear. To elucidate the molecular basis of Ces1d-dependent recognition, we semi-synthesized a glycoprobe, G1M9-va-JW972, by conjugating the Ces1d-specific inhibitor JW972 to the aglycone of G1M9 using a linker via a click reaction. In the ER-EM reaction with this probe, M8A-va-piperidine was detected as an ER-EM product with the aglycone structural conversion via Ces1d-mediated hydrolysis of the JW972 moiety, demonstrating recognition of the substrate aglycone by the Ces1d component of ER-EM complex. Inhibition of the lipolysis site of Ces1d with WWL229 significantly reduced ER-EM activity, indicating that this site is essential for recognizing hydrophobic aglycones. Furthermore, the inactive substrate GlcMan-4MU was efficiently hydrolyzed in the presence of the Ces1d lipolysis site-specific inhibitor WWL229, demonstrating that the association of the hydrophobic compound WWL229 with the Ces1d lipolysis site contributes to allosteric activation of ER-EM. Our findings provide important insights into the functional regulation of ER-EM complex, a novel therapeutic target for protein misfolding diseases. - Source: PubMed
Publication date: 2026/01/03
Taira AkitoKuribara TaikiHirose MitsuakiTotani Kiichiro - - Source: PubMed
Publication date: 2025/12/15
Chu XuanZhang LigaiXiang ShiqingHuang Yuting