ArticleThe American journal of pathology2016
Formaldehyde Is a Potent Proteotoxic Stressor Causing Rapid Heat Shock Transcription Factor 1 Activation and Lys48-Linked Polyubiquitination of Proteins.
Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Damage to newly synthesized proteins is a major cause of Cd(II) toxicity counteracted by proteasomes and integrated stress response in human cells.Chemico-biological interactions · 2026Article
- Decreasing peptide deformylase activity is a beneficial strategy for increasing formaldehyde resistance inbioRxiv : the preprint server for biology · 2026Article
- Impact of formalin gas exposure on quail testicular health in quail (Open veterinary journal · 2025Article
- The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks.Nucleic acids research · 2025Article
- Nuclear SUMOylation and Proteotoxic Stress Responses to Metals with Different Ligand Preferences.Chemical research in toxicology · 2025Article
- Monoubiquitinated H2B, a Main Chromatin Target of Formaldehyde, Is Important for S-Phase Checkpoint Signaling and Genome Stability.Molecular carcinogenesis · 2024Article
- Exogenous and endogenous formaldehyde-induced DNA damage in the aging brain: mechanisms and implications for brain diseases.Cell biology and toxicology · 2024Review
- Impact of glyphosate and glyphosate-based herbicides on phyllospheric Methylobacterium.BMC plant biology · 2024Article
- Oncoprotein SET dynamically regulates cellular stress response through nucleocytoplasmic transport in breast cancer.Cell biology and toxicology · 2023Article
- Vulnerability of HIF1α and HIF2α to damage by proteotoxic stressors.Toxicology and applied pharmacology · 2022Article
- Heat Shock Proteins and HSF1 in Cancer.Frontiers in oncology · 2022Review
- EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde.PLoS biology · 2021Article
- Formaldehyde-responsive proteins, TtmR and EfgA, reveal a tradeoff between formaldehyde resistance and efficient transition to methylotrophy inJournal of bacteriology · 2021Article
- A novel combination therapy targeting ubiquitin-specific protease 5 in MYCN-driven neuroblastoma.Oncogene · 2021Article
- The toxic side of one-carbon metabolism and epigenetics.Redox biology · 2021Article
- Global Transcriptional Response ofMicroorganisms · 2021Article
- A ubiquitin switch controls autocatalytic inactivation of the DNA-protein crosslink repair protease SPRTN.Nucleic acids research · 2021Article
- Chromosomal Organization and Regulation of Genetic Function inEcoSal Plus · 2020Article
- Article
- Toxicological Antagonism among Welding Fume Metals: Inactivation of Soluble Cr(VI) by Iron.Chemical research in toxicology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Endogenous and exogenous formaldehyde (FA) has been linked to cancer, neurotoxicity, and other pathophysiologic effects. Molecular and cellular mechanisms that underlie FA-induced damage are poorly understood. In this study, we investigated whether proteotoxicity is an important, unrecognized factor in cell injury caused by FA. We found that irrespective of their cell cycle phases, all FA-treated human cells rapidly accumulated large amounts of proteins with proteasome-targeting K48-linked polyubiquitin, which was comparable with levels of polyubiquitination in proteasome-inhibited MG132 controls. Both nuclear and cytoplasmic proteins were damaged and underwent K48-polyubiquitination. There were no significant changes in the nonproteolytic K63-polyubiquitination of soluble and insoluble cellular proteins. FA also rapidly induced nuclear accumulation and Ser326 phosphorylation of the main heat shock-responsive transcription factor HSF1, which was not a result of protein polyubiquitination. Consistent with the activation of the functional heat shock response, FA strongly elevated the expression of HSP70 genes. In contrast to the responsiveness of the cytoplasmic protein damage sensor HSF1, FA did not activate the unfolded protein response in either the endoplasmic reticulum or mitochondria. Inhibition of HSP90 chaperone activity increased the levels of K48-polyubiquitinated proteins and diminished cell viability after FA treatment. Overall, our results indicate that FA is a strong proteotoxic agent, which helps explain its diverse pathologic effects, including injury in nonproliferative tissues.
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Registered trials
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