ArticleOncogene2004
Inhibition of p53-mediated transcriptional responses by mithramycin A.
Article in Oncogene, 2004. 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, 74 citations in OpenAlex.
- The Position of Indole Methylation Controls the Structure, DNA Binding, and Cellular Functions of Mithramycin SA-Trp Analogues.Chembiochem : a European journal of chemical biology · 2025Article
- Mithramycin selectively attenuates DNA-damage-induced neuronal cell death.Cell death & disease · 2020Article
- Targeting Transcription Factors for Cancer Treatment.Molecules (Basel, Switzerland) · 2018Review
- Mithramycin A suppresses basal triple-negative breast cancer cell survival partially via down-regulating Krüppel-like factor 5 transcription by Sp1.Scientific reports · 2018Article
- An overview of recent advances in duplex DNA recognition by small molecules.Beilstein journal of organic chemistry · 2018Review
- Identification of miRNA-mRNA Modules in Colorectal Cancer Using Rough Hypercuboid Based Supervised Clustering.Scientific reports · 2017Article
- Article
- Dimerization and DNA recognition rules of mithramycin and its analogues.Journal of inorganic biochemistry · 2016Article
- Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.Scientific reports · 2014Article
- Mithramycin exerts an anti-myeloma effect and displays anti-angiogenic effects through up-regulation of anti-angiogenic factors.PloS one · 2013Article
- Human rpL3 induces G₁/S arrest or apoptosis by modulating p21 (waf1/cip1) levels in a p53-independent manner.Cell cycle (Georgetown, Tex.) · 2013Article
- A novel mithramycin analogue with high antitumor activity and less toxicity generated by combinatorial biosynthesis.Journal of medicinal chemistry · 2012Article
- Opposite effects of HIF-1α and HIF-2α on the regulation of IL-8 expression in endothelial cells.Free radical biology & medicine · 2011Article
- Combining betulinic acid and mithramycin a effectively suppresses pancreatic cancer by inhibiting proliferation, invasion, and angiogenesis.Cancer research · 2011Article
- Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening.Journal of the National Cancer Institute · 2011Article
- Opposite regulation of the human apolipoprotein M gene by hepatocyte nuclear factor 1 and Jun transcription factors.The Journal of biological chemistry · 2011Article
- Therapeutic effects of the Sp1 inhibitor mithramycin A in glioblastoma.Journal of neuro-oncology · 2011Article
- Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells.PloS one · 2011Article
- Regulation of human apolipoprotein m gene expression by orphan and ligand-dependent nuclear receptors.The Journal of biological chemistry · 2010Article
- Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers.Cancer science · 2010Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present work, we show that mithramycin A, a drug that is currently used for the treatment of patients with Paget's disease of the bone as well as with several forms of cancer, is a strong activator of the tumor suppressor p53 protein in human hepatoma cells. The time course of p53 activation by mithramycin A was similar to the known chemotherapeutic compound 5-fluorouracil (5-FU). Both 5-FU and mithramycin A induced site-specific phosphorylation of p53 at serine 15. However, in contrast to 5-FU, mithramycin A failed to activate p53 target genes including the cell cycle inhibitor p21Cip1 gene as well as the proapoptotic genes PUMA (p53-upregulated mediator of apotosis) and BAK (bcl2-homologous antagonist/killer) and blocked the induction of the above genes by 5-FU. Using transactivation assays in Sp1-deficient cells, we showed that mithramycin A inhibited the transcriptional activation of the p21Cip1 and PUMA promoters by Sp1 and p53. Using chromatin immunoprecipitation assays and a novel protein-protein interaction assay based on biotinylation in vivo, we established that 5-FU enhanced the formation of p53-Sp1 complexes in solution and the subsequent recruitment of both factors to the p21Cip1 promoter. Mithramycin A also enhanced the recruitment of p53 to the distal p21Cip1 promoter but totally blocked the recruitment of Sp1 to the proximal p21Cip1 promoter. Our findings suggest that inhibition of Sp1 binding to the promoters of several p53 target genes, such as the p21Cip1 gene as well as certain proapoptotic genes, by mithramycin A, prevents the transcriptional induction of these genes by p53 and propose a mechanism that could account for some of the tumor suppressing and antiapoptotic effects of mithramycin A.
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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.