ArticleMolecular and cellular biology2018
Induction of the p53 Tumor Suppressor in Cancer Cells through Inhibition of Cap-Dependent Translation.
Article in Molecular and cellular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Anticancer activity of an apigenin-functionalized silica-coated silver oxide nanocomposite against human gastric adenocarcinoma cells (AGS): in vitro and in silico analysis.BMC biotechnology · 2026Article
- Structural potential of the 5' noncoding regions of the mRNAs encoding p53 isoforms.Acta biochimica Polonica · 2026Review
- miRNAs that regulate apoptosis in breast cancer and cervical cancer.Cell biochemistry and biophysics · 2024Review
- Article
- Tumor Suppressor p53 Down-Regulates Programmed Cell Death Protein 4 (PDCD4) Expression.Current oncology (Toronto, Ont.) · 2023Article
- Article
- Inhibition of triple‑negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt.Oncology reports · 2022Article
- Anti‑proliferative effect of honokiol on SW620 cells through upregulating BMP7 expression via the TGF‑β1/p53 signaling pathway.Oncology reports · 2020Article
- MicroRNAs and Apoptosis in Colorectal Cancer.International journal of molecular sciences · 2020Review
- Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity.Cell reports · 2019Article
- Pro-apoptotic effects of Kangfuxin on human stomach cancer cells and its underlying mechanism.Oncology letters · 2018Article
- Cytotoxic effects of auraptene against a human malignant glioblastoma cell line.Avicenna journal of phytomedicineArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The p53 tumor suppressor plays a critical role in protecting normal cells from malignant transformation. Development of small molecules to reactivate p53 in cancer cells has been an area of intense research. We previously identified an internal ribosomal entry site (IRES) within the 5' untranslated region of p53 mRNA that mediates translation of the p53 mRNA independent of cap-dependent translation. Our results also show that in response to DNA damage, cells switch from cap-dependent translation to cap-independent translation of p53 mRNA. In the present study, we discovered a specific inhibitor of cap-dependent translation, 4EGI-1, that is capable of inducing the accumulation of p53 in cancer cells retaining wild-type p53. Our results show that 4EGI-1 causes an increase in p53 IRES activity, leading to increased translation of p53 mRNA. We also observed that 4EGI-1 induces cancer cell apoptosis in a p53-dependent manner. Furthermore, 4EGI-1 induces p53 in cancer cells without causing DNA double-strand breaks. In conclusion, we discovered a mechanistic link between inhibition of cap-dependent translation and enhanced p53 accumulation. This leads to apoptosis of cancer cells without causing collateral damage to normal cells, thus providing a novel and effective therapeutic strategy for cancer.
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Registered trials
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.