ArticleBiochimica et biophysica acta2014
Ceramide modulates pre-mRNA splicing to restore the expression of wild-type tumor suppressor p53 in deletion-mutant cancer cells.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Suppression of Glucosylceramide Synthase Reverses Drug Resistance in Cancer Cells Harboring Homozygous p53 Mutants.International journal of molecular sciences · 2026Article
- Glucosylceramide Synthase, a Key Enzyme in Sphingolipid Metabolism, Regulates Expression of Genes Accounting for Cancer Drug Resistance.International journal of molecular sciences · 2025Article
- Crosslink between p53 and metastasis: focus on epithelial-mesenchymal transition, cancer stem cell, angiogenesis, autophagy, and anoikis.Molecular biology reports · 2021Review
- Age-Related Transcriptional Deregulation of Genes Coding Synaptic Proteins in Alzheimer's Disease Murine Model: Potential Neuroprotective Effect of Fingolimod.Frontiers in molecular neuroscience · 2021Article
- Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via β-catenin-activated RNA methylation.FASEB bioAdvances · 2020Article
- Small ceramide tames big p53 mutant beast.Oncotarget · 2020Article
- Fingolimod Affects Transcription of Genes Encoding Enzymes of Ceramide Metabolism in Animal Model of Alzheimer's Disease.Molecular neurobiology · 2020Article
- Ceramide-Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations.Molecular cancer therapeutics · 2020Article
- Ubiquitin-specific peptidase 39 regulates the process of proliferation and migration of human ovarian cancer via p53/p21 pathway and EMT.Medical oncology (Northwood, London, England) · 2019Article
- An NBiochemical pharmacology · 2019Article
- Expression of the SNAI2 transcriptional repressor is regulated by CCancer biology & therapy · 2019Article
- Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis.Neoplasia (New York, N.Y.) · 2018Review
- Ceramide Signaling and p53 Pathways.Advances in cancer research · 2018Review
- Sphingolipid metabolism and drug resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2018Article
- Incorporation of Fluorescence Ceramide-Based HPLC Assay for Rapidly and Efficiently Assessing Glucosylceramide Synthase In Vivo.Scientific reports · 2017Article
- Human omental adipose-derived mesenchymal stem cell-conditioned medium alters the proteomic profile of epithelial ovarian cancer cell lines in vitro.OncoTargets and therapy · 2017Article
- Article
- Skipped BSCL2 Transcript in Celia's Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis.PloS one · 2016Article
- P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.Cell death & disease · 2015Article
- Spontaneous Transformation of Murine Oviductal Epithelial Cells: A Model System to Investigate the Onset of Fallopian-Derived Tumors.Frontiers in oncology · 2015Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Mutants of tumor suppressor p53 not only lose the activity in genome stabilizing and in tumor suppression, but also exhibit oncogenic function in cancer cells. Most efforts in restoring p53 biological activity focus on either altering mutant-protein conformation or introducing an exogenous p53 gene into cells to eliminate p53-mutant cancer cells. Being different from these, we report that ceramide can restore the expression of wild-type p53 and induce p53-dependent apoptosis in deletion-mutant cancer cells. We show that endogenous long-carbon chain ceramide species (C16- to C24-ceramides) and exogenous C6-ceramide, rather than other sphingolipids, restore wild-type mRNA (intact exon-5), phosphorylated protein (Ser15 in exon-5) of p53, and p53-responsive proteins, including p21 and Bax, in ovarian cancer cells, which predominantly express a deleted exon-5 of p53 mutant before treatments. Consequently, the restored p53 sensitizes these p53-mutant cancer cells to DNA damage-induced growth arrest and apoptosis. Furthermore, we elucidate that ceramide activates protein phosphatase-1, and then the dephosphorylated serine/arginine-rich splicing-factor 1 (SRSF1) is translocated to the nucleus, thus promoting pre-mRNA splicing preferentially to wild-type p53 expression. These findings disclose an unrecognized mechanism that pre-mRNA splicing dysfunction can result in p53 deletion-mutants. Ceramide through SRSF1 restores wild-type p53 expression versus deletion-mutant and leads cancer cells to apoptosis. This suggests that heterozygous deletion-mutants of p53 can be restored in posttranscriptional level by using epigenetic approaches.
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