ArticleNature communications2018
NEDDylation promotes nuclear protein aggregation and protects the Ubiquitin Proteasome System upon proteotoxic stress.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 99 citations in OpenAlex.
- Article
- A tale of dual role: HECT‑type E3 ubiquitin ligase mechanisms in liver diseases (Review).International journal of molecular medicine · 2026Review
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.Essays in biochemistry · 2025Review
- Characterization of the Intact Proteomic Profile of Senescent-Associated Secretory Phenotype by Top-Down Mass Spectrometry.Analytical chemistry · 2025Article
- Article
- HUWE1 stimulates mTORC1 activity by enhancing Rheb interaction with mTORC1 and supports de novo pyrimidine synthesis.Cell reports · 2025Article
- Neddylation regulates the development and function of glutamatergic neurons.Communications biology · 2025Article
- Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.Scientific reports · 2025Article
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- A nuclear protein quality control system for elimination of nucleolus-related inclusions.The EMBO journal · 2025Article
- Article
- Neddylation inhibition prevents acetaminophen-induced liver damage by enhancing the anabolic cardiolipin pathway.Cell reports. Medicine · 2024Article
- Substrate and Functional Diversity of Protein Lysine Post-translational Modifications.Genomics, proteomics & bioinformatics · 2024Review
- Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer.Nature communications · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- Improving homology-directed repair by small molecule agents for genetic engineering in unconventional yeast?-Learning from the engineering of mammalian systems.Microbial biotechnology · 2024Review
- A dicer-related helicase opposes the age-related pathology from SKN-1 activation in ASI neurons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Effects of neddylation on viral infection: an overview.Archives of virology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spatial management of stress-induced protein aggregation is an integral part of the proteostasis network. Protein modification by the ubiquitin-like molecule NEDD8 increases upon proteotoxic stress and it is characterised by the formation of hybrid NEDD8/ubiquitin conjugates. However, the biological significance of this response is unclear. Combination of quantitative proteomics with biological analysis shows that, during proteotoxic stress, NEDDylation promotes nuclear protein aggregation, including ribosomal proteins as a major group. This correlates with protection of the nuclear Ubiquitin Proteasome System from stress-induced dysfunction. Correspondingly, we show that NEDD8 compromises ubiquitination and prevents targeting and processing of substrates by the proteasome. Moreover, we identify HUWE1 as a key E3-ligase that is specifically required for NEDDylation during proteotoxic stress. The study reveals a specific role for NEDD8 in nuclear protein aggregation upon stress and is consistent with the concept that transient aggregate formation is part of a defence mechanism against proteotoxicity.
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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.