ArticleThe Journal of biological chemistry2011
Caspase-mediated cleavage of RNA-binding protein HuR regulates c-Myc protein expression after hypoxic stress.
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 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- A unified therapeutic theory for treating cancer via master regulators of the universal apoptosis network.Cell death discovery · 2026Review
- Structural, biological, and biomedical implications of mRNA interactions with the master regulator HuR.NAR molecular medicine · 2025Review
- An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR.Cell death discovery · 2024Article
- Intronic RNA secondary structural information captured for the humanNAR genomics and bioinformatics · 2024Article
- PRMT5-mediated arginine methylation of FXR1 is essential for RNA binding in cancer cells.Nucleic acids research · 2024Article
- RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma.Oral oncology reports · 2024Article
- Heat shock response during the resolution of inflammation and its progressive suppression in chronic-degenerative inflammatory diseases.Cell stress & chaperones · 2024Review
- An AKT1-and TRIM21-mediated phosphodegron controls proteasomal degradation of HuR enabling cell survival under heat shock.iScience · 2023Article
- CRC-derived exosomes containing the RNA binding protein HuR promote lung cell proliferation by stabilizing c-Myc mRNA.Cancer biology & therapy · 2022Article
- HuR as a molecular target for cancer therapeutics and immune-related disorders.Advanced drug delivery reviews · 2022Review
- The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.Advanced drug delivery reviews · 2022Review
- The RNA-binding protein HuR is required for maintenance of the germinal centre response.Nature communications · 2021Article
- Targeting the RNA-Binding Protein HuR as Potential Thera-Peutic Approach for Neurological Disorders: Focus on Amyo-Trophic Lateral Sclerosis (ALS), Spinal Muscle Atrophy (SMA) and Multiple Sclerosis.International journal of molecular sciences · 2021Review
- Innate immunity, inflammation activation and heat-shock protein in COVID-19 pathogenesis.Journal of neuroimmunology · 2021Review
- ELAVL1 primarily couples mRNA stability with the 3' UTRs of interferon-stimulated genes.Cell reports · 2021Article
- A Novel Role of SLC26A3 in the Maintenance of Intestinal Epithelial Barrier Integrity.Gastroenterology · 2021Article
- A macrophage-specific lncRNA regulates apoptosis and atherosclerosis by tethering HuR in the nucleus.Nature communications · 2020Article
- Suppressed anti-inflammatory heat shock response in high-risk COVID-19 patients: lessons from basic research (inclusive bats), light on conceivable therapies.Clinical science (London, England : 1979) · 2020Review
- GRK2-Dependent HuR Phosphorylation Regulates HIF1α Activation under Hypoxia or Adrenergic Stress.Cancers · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Altered expression of RNA-binding proteins modulates gene expression in association with mRNAs encoding many proto-oncogenes, cytokines, chemokines, and proinflammatory factors. Hu antigen R (HuR), a ubiquitously expressed protein, controls a range of cellular functions such as tumor progression, apoptosis, invasion, and metastasis by stabilizing the AU-rich element located at the 3'-untranslated region (UTR) of target mRNAs. Although significant progress has been made in understanding HuR regulation in gene expression, little is known about how HuR undergoes post-translational modifications and recruits target mRNAs during hypoxic stress. Here, we report that during CoCl(2)-induced hypoxic stress, HuR is significantly overexpressed and undergoes caspase-dependent cleavage in head and neck squamous cell carcinoma cells. Unexpectedly, the HuR-cleavage product 1 (HuR-CP1) was found to strongly associate with the 3'-UTR of c-myc mRNA and block mRNA translation. The binding efficiency of HuR to the 3'-UTR of c-myc mRNA was confirmed using ribonucleoprotein immunoprecipitation and site-directed mutagenesis at the AU-rich element sequences of the c-myc mRNA. Overexpression of a non-cleavable isoform, HuR-D226A, revealed a potent dominant-negative effect, repressing cleavage of endogenous HuR and promoting cell viability. Surprisingly, under hypoxia, siRNA knockdown of HuR elevated c-Myc protein expression. These findings suggest an important role for HuR in hypoxia, and we may have revealed a novel post-transcriptional mechanism that controls c-Myc expression in oral cancer progression.
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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.