ArticleThe Journal of biological chemistry2015
Long Term Aggresome Accumulation Leads to DNA Damage, p53-dependent Cell Cycle Arrest, and Steric Interference in Mitosis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- iPAR: a new reporter for eukaryotic cytoplasmic protein aggregation.BMC methods · 2025Article
- Missense Mutations in Myc Box I Influence Nucleocytoplasmic Transport to Promote Leukemogenesis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis.The EMBO journal · 2021Review
- Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery.Redox biology · 2020Article
- Chromatin accessibility and transcription dynamics during in vitro astrocyte differentiation of Huntington's Disease Monkey pluripotent stem cells.Epigenetics & chromatin · 2019Article
- Rat Glioma Cell-Based Functional Characterization of Anti-Stress and Protein Deaggregation Activities in the Marine Carotenoids, Astaxanthin and Fucoxanthin.Marine drugs · 2019Article
- Loss of a proteostatic checkpoint in intestinal stem cells contributes to age-related epithelial dysfunction.Nature communications · 2019Article
- Structural progression of amyloid-β Arctic mutant aggregation in cells revealed by multiparametric imaging.The Journal of biological chemistry · 2019Article
- Live-cell super-resolution microscopy reveals a primary role for diffusion in polyglutamine-driven aggresome assembly.The Journal of biological chemistry · 2019Article
- A patient-derived cellular model for Huntington's disease reveals phenotypes at clinically relevant CAG lengths.Molecular biology of the cell · 2018Article
- Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines.Food science & nutrition · 2018Article
- Fluorescence Self-Quenching from Reporter Dyes Informs on the Structural Properties of Amyloid Clusters Formed in Vitro and in Cells.Nano letters · 2017Article
- Expression of the type VI intermediate filament proteins CP49 and filensin in the mouse lens epithelium.Molecular vision · 2016Article
- p53-Induced Autophagy Regulates Chemotherapy and Radiotherapy Resistance in Multidrug Resistance Cancer Cells.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Juxtanuclear aggresomes form in cells when levels of aggregation-prone proteins exceed the capacity of the proteasome to degrade them. It is widely believed that aggresomes have a protective function, sequestering potentially damaging aggregates until these can be removed by autophagy. However, most in-cell studies have been carried out over a few days at most, and there is little information on the long term effects of aggresomes. To examine these long term effects, we created inducible, single-copy cell lines that expressed aggregation-prone polyglutamine proteins over several months. We present evidence that, as perinuclear aggresomes accumulate, they are associated with abnormal nuclear morphology and DNA double-strand breaks, resulting in cell cycle arrest via the phosphorylated p53 (Ser-15)-dependent pathway. Further analysis reveals that aggresomes can have a detrimental effect on mitosis by steric interference with chromosome alignment, centrosome positioning, and spindle formation. The incidence of apoptosis also increased in aggresome-containing cells. These severe defects developed gradually after juxtanuclear aggresome formation and were not associated with small cytoplasmic aggregates alone. Thus, our findings demonstrate that, in dividing cells, aggresomes are detrimental over the long term, rather than protective. This suggests a novel mechanism for polyglutamine-associated developmental and cell biological abnormalities, particularly those with early onset and non-neuronal pathologies.
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