ArticleThe Journal of biological chemistry2014
The proteasome inhibitor bortezomib is a potent inducer of zinc finger AN1-type domain 2a gene expression: role of heat shock factor 1 (HSF1)-heat shock factor 2 (HSF2) heterocomplexes.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- More than the 'master regulator of cytosolic proteostasis': new roles for HSF1 in promoting tissue health.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- A guide to heat shock factors as multifunctional transcriptional regulators.The FEBS journal · 2025Review
- HSF1 Activation Mechanisms, Disease Roles, and Small Molecule Therapeutics.International journal of biological sciences · 2025Review
- Multi-omics profiling of DNA methylation and gene expression alterations in human cocaine use disorder.Translational psychiatry · 2024Article
- Human coronaviruses activate and hijack the host transcription factor HSF1 to enhance viral replication.Cellular and molecular life sciences : CMLS · 2024Article
- Comprehensive Structure-Activity Relationship Studies of Cepafungin Enabled by Biocatalytic C-H Oxidations.ACS central science · 2023Article
- CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder.Nature communications · 2022Article
- 26S proteasomes become stably activated upon heat shock when ubiquitination and protein degradation increase.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- An Arsenite Relay between PSMD14 and AIRAP Enables Revival of Proteasomal DUB Activity.Biomolecules · 2021Article
- Copper toxicity of inflection point in human intestinal cell line Caco-2 dissected: influence of temporal expression patterns.In vitro cellular & developmental biology. Animal · 2021Article
- The proteostasis guardian HSF1 directs the transcription of its paralog and interactor HSF2 during proteasome dysfunction.Cellular and molecular life sciences : CMLS · 2021Article
- AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion.Nature communications · 2020Article
- Quantitative and multiplexed chemical-genetic phenotyping in mammalian cells with QMAP-Seq.Nature communications · 2020Article
- HSF1 inhibition attenuates HIV-1 latency reversal mediated by several candidate LRAs In Vitro and Ex Vivo.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Insights into high-pressure acclimation: comparative transcriptome analysis of sea cucumber Apostichopus japonicus at different hydrostatic pressure exposures.BMC genomics · 2020Article
- Tailoring of Proteostasis Networks with Heat Shock Factors.Cold Spring Harbor perspectives in biology · 2019Review
- ZFAND5/ZNF216 is an activator of the 26S proteasome that stimulates overall protein degradation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Nitazoxanide inhibits paramyxovirus replication by targeting the Fusion protein folding: role of glycoprotein-specific thiol oxidoreductase ERp57.Scientific reports · 2018Article
- PRDM14 directly interacts with heat shock proteins HSP90α and glucose-regulated protein 78.Cancer science · 2018Article
- Bortezomib-induced heat shock response protects multiple myeloma cells and is activated by heat shock factor 1 serine 326 phosphorylation.Oncotarget · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The zinc finger AN1-type domain 2a gene, also known as arsenite-inducible RNA-associated protein (AIRAP), was recently identified as a novel human canonical heat shock gene strictly controlled by heat shock factor (HSF) 1. Little is known about AIRAP gene regulation in human cells. Here we report that bortezomib, a proteasome inhibitor with anticancer and antiangiogenic properties used in the clinic for treatment of multiple myeloma, is a potent inducer of AIRAP expression in human cells. Using endothelial cells as a model, we unraveled the molecular mechanism regulating AIRAP expression during proteasome inhibition. Bortezomib induces AIRAP expression at the transcriptional level early after treatment, concomitantly with polyubiquitinated protein accumulation and HSF activation. AIRAP protein is detected at high levels for at least 48 h after bortezomib exposure, together with the accumulation of HSF2, a factor implicated in differentiation and development regulation. Different from heat-mediated induction, in bortezomib-treated cells, HSF1 and HSF2 interact directly, forming HSF1-HSF2 heterotrimeric complexes recruited to a specific heat shock element in the AIRAP promoter. Interestingly, whereas HSF1 has been confirmed to be critical for AIRAP gene transcription, HSF2 was found to negatively regulate AIRAP expression after bortezomib treatment, further emphasizing an important modulatory role of this transcription factor under stress conditions. AIRAP function is still not defined. However, the fact that AIRAP is expressed abundantly in primary human cells at bortezomib concentrations comparable with plasma levels in treated patients suggests that AIRAP may participate in the regulatory network controlling proteotoxic stress during bortezomib treatment.
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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.