ArticleThe Journal of biological chemistry2011
4-Phenylbutyrate stimulates Hsp70 expression through the Elp2 component of elongator and STAT-3 in cystic fibrosis epithelial cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.Muscle & nerve · 2021Trial
- Real-World Clinical Experience With Sodium Phenylbutyrate and Taurursodiol at a Single Amyotrophic Lateral Sclerosis Center in the United States.European journal of neurology · 2025Article
- Pharmacological Intervention with 4-Phenylbutyrate Ameliorates TiAl6V4 Nanoparticles-Induced Inflammatory Osteolysis by Promoting Macrophage Apoptosis.Bioengineering (Basel, Switzerland) · 2025Article
- Inhibition of SOD1 trimerization is a novel drug target for ALS disease.Translational neurodegeneration · 2025Article
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- New Approved Drugs Appearing in the Pharmaceutical Market in 2022 Featuring Fragments of Tailor-Made Amino Acids and Fluorine.Molecules (Basel, Switzerland) · 2023Review
- Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation.Nature reviews. Drug discovery · 2023Review
- Article
- Status of ALS Treatment, Insights into Therapeutic Challenges and Dilemmas.Journal of personalized medicine · 2022Review
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Article
- The Role of PERK in Understanding Development of Neurodegenerative Diseases.International journal of molecular sciences · 2021Review
- Small Hsps as Therapeutic Targets of Cystic Fibrosis Transmembrane Conductance Regulator Protein.International journal of molecular sciences · 2021Review
- Decrypting the crosstalk of noncoding RNAs in the progression of IPF.Molecular biology reports · 2020Review
- Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.International journal of molecular sciences · 2020Review
- The Probable, Possible, and Novel Functions of ERp29.Frontiers in physiology · 2020Article
- The KDEL receptor has a role in the biogenesis and trafficking of the epithelial sodium channel (ENaC).The Journal of biological chemistry · 2019Article
- How to rescue misfolded SERT, DAT and NET: targeting conformational intermediates with atypical inhibitors and partial releasers.Biochemical Society transactions · 2019Review
- Potential regulatory role of circular RNA in idiopathic pulmonary fibrosis.International journal of molecular medicine · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Sodium 4-phenylbutyrate (4PBA) corrects trafficking of ΔF508-CFTR in Cystic Fibrosis (CF) epithelia, which is hypothesized to, at least in part, result from increased expression of Hsp70 (stress-induced 70 kDa heat shock protein). To identify other 4PBA-regulated proteins that may promote correction of ΔF508 trafficking, we performed differential display RT-PCR on mRNA from IB3-1 CF bronchiolar epithelial cells treated for 0-24 h with 1 mM 4PBA. In this screen, a STAT-3 (signal transducer and activator of transcription-3)-interacting protein, StIP-1 that regulates STAT-3 activation had transiently increased expression. StIP-1 is identical to Elongator protein 2 (Elp2), a component of the Elongator complex that regulates RNA polymerase II. Previous studies have suggested that Elongator regulates Hsp70 mRNA transcription, and that the Hsp70 promoter contains functional STAT-3-binding sites. We therefore tested the hypothesis that 4PBA increases Hsp70 expression by an Elongator- and STAT-3-dependent mechanism. 4PBA treatment of IB3-1 CF bronchiolar epithelial cells caused transiently increased expression of Hsp70 protein, as well as Elp2 protein and mRNA. Elp2 depletion by transfection of small interfering RNAs, reduced both Elp2 and Hsp70 protein expression. 4PBA also caused transient activation of STAT-3, and increased abundance of nuclear proteins that bind to the STAT-3-responsive element of the Hsp70 promoter. Luciferase reporter assays demonstrated that both Elp2 overexpression and 4PBA increase Hsp70 promoter activity, while Elp2 depletion blocked the ability of 4PBA to stimulate Hsp70 promoter activity. Together, these data suggest that Elp2 and STAT-3 mediate, at least in part, the stimulation of Hsp70 expression by 4PBA.
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Registered trials
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