ArticleMolecular cell2019
Dual Role of Ribosome-Binding Domain of NAC as a Potent Suppressor of Protein Aggregation and Aging-Related Proteinopathies.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Proteostasis and ageing dissidence.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Chaperone-mediated remodelling of mutant huntingtin.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- NAC promotes co-translational protein folding at the ribosomal tunnel exit.Molecular cell · 2026Article
- Article
- Structural basis of co-translational N-myristoylation in humans.Nature communications · 2026Article
- Comparative transcriptomic analysis of retinal response to diverse cellular stresses reveals relative contributions of different cell death processes and signalling networks.Cell death & disease · 2025Article
- Mechanistic Insights into Protein Biogenesis and Maturation on the Ribosome.Journal of molecular biology · 2025Review
- An Orthogonal Supramolecular Approach toward Protein Binding and Protein Sensing Using Dendrimers as Scaffolds for the Noncovalent Assembly of Binding and Sensing Groups.ACS materials Au · 2025Article
- Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin.Nature communications · 2025Article
- Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis.Nature communications · 2024Article
- Disruption of the nascent polypeptide-associated complex leads to reduced polyglutamine aggregation and toxicity.PloS one · 2024Article
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- Proteomic association with age-dependent sex differences in Wisconsin Card Sorting Test performance in healthy Thai subjects.Scientific reports · 2023Article
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA.Nucleic acids research · 2022Article
- Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT.Nature communications · 2022Article
- Article
- Extended disordered regions of ribosome-associated NAC proteins paralogs belong only to the germline in Drosophila melanogaster.Scientific reports · 2022Article
- Fidelity of Cotranslational Protein Targeting to the Endoplasmic Reticulum.International journal of molecular sciences · 2021Review
- RACK1 modulates polyglutamine-induced neurodegeneration by promoting ERK degradation in Drosophila.PLoS genetics · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
The nascent polypeptide-associated complex (NAC) is a conserved ribosome-associated protein biogenesis factor. Whether NAC exerts chaperone activity and whether this function is restricted to de novo protein synthesis is unknown. Here, we demonstrate that NAC directly exerts chaperone activity toward structurally diverse model substrates including polyglutamine (PolyQ) proteins, firefly luciferase, and Aβ40. Strikingly, we identified the positively charged ribosome-binding domain in the N terminus of the βNAC subunit (N-βNAC) as a major chaperone entity of NAC. N-βNAC by itself suppressed aggregation of PolyQ-expanded proteins in vitro, and the positive charge of this domain was critical for this activity. Moreover, we found that NAC also exerts a ribosome-independent chaperone function in vivo. Consistently, we found that a substantial fraction of NAC is non-ribosomal bound in higher eukaryotes. In sum, NAC is a potent suppressor of aggregation and proteotoxicity of mutant PolyQ-expanded proteins associated with human diseases like Huntington's disease and spinocerebellar ataxias.
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