ArticleThe Journal of cell biology2012
Indirect inhibition of 26S proteasome activity in a cellular model of Huntington's disease.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 172 citations in OpenAlex.
- Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease.EMBO molecular medicine · 2026Article
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Nuclear poly-glutamine aggregates rupture the nuclear envelope and hinder its repair.The Journal of cell biology · 2024Article
- Sphingosine kinase 2 regulates protein ubiquitination networks in neurons.Molecular and cellular neurosciences · 2024Article
- Role of TFEB in Huntington's Disease.Biology · 2024Review
- Sequestrase chaperones protect against oxidative stress-induced protein aggregation and [PSI+] prion formation.PLoS genetics · 2024Article
- Mechanisms of ubiquitin-independent proteasomal degradation and their roles in age-related neurodegenerative disease.Frontiers in cell and developmental biology · 2024Review
- Targeting Proteasomes and the MHC Class I Antigen Presentation Machinery to Treat Cancer, Infections and Age-Related Diseases.Cancers · 2023Review
- Neuroprotective effects of hepatoma-derived growth factor in models of Huntington's disease.Life science alliance · 2023Article
- Proteotoxic stresses stimulate dissociation of UBL4A from the tail-anchored protein recognition complex.The Biochemical journal · 2023Article
- Brain-Derived 11S Regulator (PA28αβ) Promotes Proteasomal Hydrolysis of Elongated Oligoglutamine-Containing Peptides.International journal of molecular sciences · 2023Article
- Cell Rearrangement and Oxidant/Antioxidant Imbalance in Huntington's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Advances in Proteasome Enhancement by Small Molecules.Biomolecules · 2021Review
- Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties.Nature communications · 2021Article
- Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease.The EMBO journal · 2021Article
- Praja1 ubiquitin ligase facilitates degradation of polyglutamine proteins and suppresses polyglutamine-mediated toxicity.Molecular biology of the cell · 2021Article
- The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin.Biomolecules · 2020Article
- Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition.Epigenetics & chromatin · 2020Article
- A role of cellular translation regulation associated with toxic Huntingtin protein.Cellular and molecular life sciences : CMLS · 2020Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Pathognomonic accumulation of ubiquitin (Ub) conjugates in human neurodegenerative diseases, such as Huntington's disease, suggests that highly aggregated proteins interfere with 26S proteasome activity. In this paper, we examine possible mechanisms by which an N-terminal fragment of mutant huntingtin (htt; N-htt) inhibits 26S function. We show that ubiquitinated N-htt-whether aggregated or not-did not choke or clog the proteasome. Both Ub-dependent and Ub-independent proteasome reporters accumulated when the concentration of mutant N-htt exceeded a solubility threshold, indicating that stabilization of 26S substrates is not linked to impaired Ub conjugation. Above this solubility threshold, mutant N-htt was rapidly recruited to cytoplasmic inclusions that were initially devoid of Ub. Although synthetically polyubiquitinated N-htt competed with other Ub conjugates for access to the proteasome, the vast majority of mutant N-htt in cells was not Ub conjugated. Our data confirm that proteasomes are not directly impaired by aggregated N-terminal fragments of htt; instead, our data suggest that Ub accumulation is linked to impaired function of the cellular proteostasis network.
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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.