ArticlePloS one2011
p21(WAF1/CIP1) upregulation through the stress granule-associated protein CUGBP1 confers resistance to bortezomib-mediated apoptosis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 94 citations in OpenAlex.
- Modulation of TNF-α mRNA stability by human antigen R and miR181s in sepsis-induced immunoparalysis.EMBO molecular medicine · 2015Trial
- Loss of O-GlcNAc transferase activity impairs the dynamic formation of protective stress granules in ischemic cardiomyocytes.The Biochemical journal · 2026Article
- Review
- Stress granules promote quiescence by enhancing p21 levels and reducing phospho-Rb.RNA (New York, N.Y.) · 2025Article
- RNF144A-VRK2-G3BP1 axis regulates stress granule assembly.Cell death discovery · 2025Article
- Long non-coding RNA generated from CDKN1A gene by alternative polyadenylation regulates p21 expression during DNA damage response.Nucleic acids research · 2023Article
- Stress granules dynamics: benefits in cancer.BMB reports · 2022Review
- An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma.Cell death & disease · 2022Article
- Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A.iScience · 2022Article
- Glucocorticoids enhance chemotherapy-driven stress granule assembly and impair granule dynamics, leading to cell death.Journal of cell science · 2022Article
- CELF1 represses Doublesex1 expression via its 5' UTR in the crustacean Daphnia magna.PloS one · 2022Article
- Paclitaxel-induced stress granules increaseJournal of biomedical research · 2021Article
- CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis.International journal of molecular sciences · 2021Review
- Biomolecular Condensates and Cancer.Cancer cell · 2021Review
- Stress Granules in the Anti-Cancer Medications Mechanism of Action: A Systematic Scoping Review.Frontiers in oncology · 2021Article
- Stress Granules Involved in Formation, Progression and Metastasis of Cancer: A Scoping Review.Frontiers in cell and developmental biology · 2021Article
- Revisiting the Concept of Stress in the Prognosis of Solid Tumors: A Role for Stress Granules Proteins?Cancers · 2020Review
- Understanding the roles of stress granule during chemotherapy for patients with malignant tumors.American journal of cancer research · 2020Review
- Treatment of cancer cells with Lapatinib negatively regulates general translation and induces stress granules formation.PloS one · 2020Article
- RNA-binding protein CELF6 is cell cycle regulated and controls cancer cell proliferation by stabilizing p21.Cell death & disease · 2019Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundp21(WAF1/CIP1) is a well known cyclin-dependent kinase inhibitor induced by various stress stimuli. Depending on the stress applied, p21 upregulation can either promote apoptosis or prevent against apoptotic injury. The stress-mediated induction of p21 involves not only its transcriptional activation but also its posttranscriptional regulation, mainly through stabilization of p21 mRNA levels. We have previously reported that the proteasome inhibitor MG132 induces the stabilization of p21 mRNA, which correlates with the formation of cytoplasmic RNA stress granules. The mechanism underlying p21 mRNA stabilization, however, remains unknown. METHODOLOGY/PRINCIPAL
findingsWe identified the stress granules component CUGBP1 as a factor required for p21 mRNA stabilization following treatment with bortezomib ( = PS-341/Velcade). This peptide boronate inhibitor of the 26S proteasome is very efficient for the treatment of myelomas and other hematological tumors. However, solid tumors are sometimes refractory to bortezomib treatment. We found that depleting CUGBP1 in cancer cells prevents bortezomib-mediated p21 upregulation. FISH experiments combined to mRNA stability assays show that this effect is largely due to a mistargeting of p21 mRNA in stress granules leading to its degradation. Altering the expression of p21 itself, either by depleting CUGBP1 or p21, promotes bortezomib-mediated apoptosis. CONCLUSIONS/SIGNIFICANCE: We propose that one key mechanism by which apoptosis is inhibited upon treatment with chemotherapeutic drugs might involve upregulation of the p21 protein through CUGBP1.
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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.