ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Disruption of N-linked glycosylation promotes proteasomal degradation of the human ATP-binding cassette transporter ABCA3.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Lentiviral-mediated gene complementation to rescue pathogenic ABCA3 variants.American journal of respiratory cell and molecular biology · 2026Article
- Lentiviral-mediated gene complementation rescues pathogenicbioRxiv : the preprint server for biology · 2025Article
- Cyclosporine A in children with ABCA3 deficiency.Pediatric pulmonology · 2024Article
- Review
- ABCA3 Deficiency-Variant-Specific Response to Hydroxychloroquine.International journal of molecular sciences · 2023Article
- Quantifying Functional Impairment ofInternational journal of molecular sciences · 2023Article
- Gene Therapeutics for Surfactant Dysfunction Disorders: Targeting the Alveolar Type 2 Epithelial Cell.Human gene therapy · 2022Review
- Cryo-EM structures of the human surfactant lipid transporter ABCA3.Science advances · 2022Article
- N-glycosylation of UNC93B1 at a Specific Asparagine Residue Is Required for TLR9 Signaling.Frontiers in immunology · 2022Article
- Functional Genomics ofAmerican journal of respiratory cell and molecular biology · 2020Article
- Functional characterization of four ATP-binding cassette transporter A3 gene (ABCA3) variants.Human mutation · 2020Article
- An N-Glycosylated Form of SERINC5 Is Specifically Incorporated into HIV-1 Virions.Journal of virology · 2018Article
- The classification of ATP-binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system.Pediatric investigation · 2018Article
- The biology of the ABCA3 lipid transporter in lung health and disease.Cell and tissue research · 2017Review
- Article
- GlycoMineScientific reports · 2016Article
- Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases.PloS one · 2016Article
- Lost after translation: insights from pulmonary surfactant for understanding the role of alveolar epithelial dysfunction and cellular quality control in fibrotic lung disease.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- A non-BRICHOS SFTPC mutant (SP-CI73T) linked to interstitial lung disease promotes a late block in macroautophagy disrupting cellular proteostasis and mitophagy.American journal of physiology. Lung cellular and molecular physiology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The lipid transport protein, ABCA3, expressed in alveolar type 2 (AT2) cells, is critical for surfactant homeostasis. The first luminal loop of ABCA3 contains three putative N-linked glycosylation sites at residues 53, 124, and 140. A common cotranslational modification, N-linked glycosylation, is critical for the proper expression of glycoproteins by enhancing folding, trafficking, and stability through augmentation of the endoplasmic reticulum (ER) folding cycle. To understand its role in ABCA3 biosynthesis, we utilized EGFP-tagged fusion constructs with either wild-type or mutant ABCA3 cDNAs that contained glutamine for asparagine substitutions at the putative glycosylation motifs. In A549 cells, inhibition of glycosylation by tunicamycin increased the electrophoretic mobility (Mr) and reduced the expression level of wild-type ABCA3 in a dose-dependent manner. Fluorescence imaging of transiently transfected A549 or primary human AT2 cells showed that although single motif mutants exhibited a vesicular distribution pattern similar to wild-type ABCA3, mutation of N124 and N140 residues resulted in a shift toward an ER-predominant distribution. By immunoblotting, the N53 mutation exhibited no effect on either the Mr or ABCA3 expression level. In contrast, substitutions at N124 or N140, as well a N124/N140 double mutation, resulted in increased electrophoretic mobility indicative of a glycosylation deficiency accompanied by reduced overall expression levels. Diminished steady-state levels of glycan-deficient ABCA3 isoforms were rescued by treatment with the proteasome inhibitor MG132. These results suggest that cotranslational N-linked glycosylation at N124 and N140 is critical for ABCA3 stability, and its disruption results in protein destabilization and proteasomal degradation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.