ArticleInternational journal of molecular sciences2022
Reduced DNAJC3 Expression Affects Protein Translocation across the ER Membrane and Attenuates the Down-Modulating Effect of the Translocation Inhibitor Cyclotriazadisulfonamide.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Macrophage-Derived Extracellular Vesicles Deliver Progranulin to Alleviate Skin Wound Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum.International journal of molecular sciences · 2025Review
- Inhibition of TSH Receptor Expression by a Cyclotriazadisulfonamide as a Potential Treatment of Graves Hyperthyroidism.Endocrinology · 2025Article
- The Role of TIM-1 and CD300a in Zika Virus Infection Investigated with Cell-Based Electrical Impedance.Biosensors · 2024Article
- Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by BiallelicInternational journal of molecular sciences · 2024Article
- Classification of subtypes and identification of dysregulated genes in sepsis.Frontiers in cellular and infection microbiology · 2023Article
- Regulation of Translation, Translocation, and Degradation of Proteins at the Membrane of the Endoplasmic Reticulum.International journal of molecular sciences · 2022Review
- Mechanisms of ER Protein Import.International journal of molecular sciences · 2022Article
- Signal Peptide Features Determining the Substrate Specificities of Targeting and Translocation Components in Human ER Protein Import.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
One of the reported substrates for the endoplasmic reticulum (ER) translocation inhibitor cyclotriazadisulfonamide (CADA) is DNAJC3, a chaperone of the unfolded protein response during ER stress. In this study, we investigated the impact of altered DNAJC3 protein levels on the inhibitory activity of CADA. By comparing WT DNAJC3 with a CADA-resistant DNAJC3 mutant, we observed the enhanced sensitivity of human CD4, PTK7 and ERLEC1 for CADA when DNAJC3 was expressed at high levels. Combined treatment of CADA with a proteasome inhibitor resulted in synergistic inhibition of protein translocation and in the rescue of a small preprotein fraction, which presumably corresponds to the CADA affected protein fraction that is stalled at the Sec61 translocon. We demonstrate that DNAJC3 enhances the protein translation of a reporter protein that is expressed downstream of the CADA-stalled substrate, suggesting that DNAJC3 promotes the clearance of the clogged translocon. We propose a model in which a reduced DNAJC3 level by CADA slows down the clearance of CADA-stalled substrates. This results in higher residual translocation into the ER lumen due to the longer dwelling time of the temporarily stalled substrates in the translocon. Thus, by directly reducing DNAJC3 protein levels, CADA attenuates its net down-modulating effect on its substrates.
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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.