ArticleOncogene2013
p53 is activated in response to disruption of the pre-mRNA splicing machinery.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 90 citations in OpenAlex.
- Pharmacological targeting of SF3a1-MDM4 splicing vulnerability in ovarian cancer with rifaximin and antisense oligonucleotide.Journal of translational medicine · 2026Article
- CDK11 inhibition induces cytoplasmic p21Molecular oncology · 2026Article
- NetCrafter: ontology-derived gene network modeling and functional interpretation.Briefings in bioinformatics · 2026Article
- Fbrsl1 is required for cranial neural crest development and reflects a conserved function of the human disease-associated protein.Disease models & mechanisms · 2025Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.Disease models & mechanisms · 2024Article
- USP39 attenuates the antitumor activity of cisplatin on colon cancer cells dependent on p53.Cell biology and toxicology · 2023Article
- The emerging significance of splicing in vertebrate development.Development (Cambridge, England) · 2022Review
- Article
- Modulation of RNA splicing associated with Wnt signaling pathway using FD-895 and pladienolide B.Aging · 2022Article
- 6-Shogaol Inhibits Oxidative Stress-Induced Rat Vascular Smooth Muscle Cell Apoptosis by Regulating OXR1-p53 Axis.Frontiers in molecular biosciences · 2022Article
- The spliceosome factor sart3 regulates hematopoietic stem/progenitor cell development in zebrafish through the p53 pathway.Cell death & disease · 2021Article
- USP39 promotes malignant proliferation and angiogenesis of renal cell carcinoma by inhibiting VEGF-ACancer cell international · 2021Article
- The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output.Science advances · 2021Article
- MDM4 alternative splicing and implication in MDM4 targeted cancer therapies.American journal of cancer research · 2021Review
- Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway.International journal of molecular sciences · 2020Article
- Runt-related transcription factor 1 is required for murine osteoblast differentiation and bone formation.The Journal of biological chemistry · 2020Article
- Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines.Investigational new drugs · 2020Article
- Cancer Cells Employ Nuclear Caspase-8 to Overcome the p53-Dependent G2/M Checkpoint through Cleavage of USP28.Molecular cell · 2020Article
- The RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing.Journal of molecular cell biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In this study, we show that interfering with the splicing machinery results in activation of the tumour-suppressor p53. The spliceosome was targeted by small interfering RNA-mediated knockdown of proteins associated with different small nuclear ribonucleoprotein complexes and by using the small-molecule splicing modulator TG003. These interventions cause: the accumulation of p53, an increase in p53 transcriptional activity and can result in p53-dependent G(1) cell cycle arrest. Mdm2 and MdmX are two key repressors of p53. We show that a decrease in MdmX protein level contributes to p53 activation in response to targeting the spliceosome. Interfering with the spliceosome also causes an increase in the rate of degradation of Mdm2. Alterations in splicing are linked with tumour development. There are frequently global changes in splicing in cancer. Our study suggests that p53 activation could participate in protection against potential tumour-promoting defects in the spliceosome. A number of known p53-activating agents affect the splicing machinery and this could contribute to their ability to upregulate p53. Preclinical studies indicate that tumours can be more sensitive than normal cells to small-molecule spliceosome inhibitors. Activation of p53 could influence the selective anti-tumour activity of this therapeutic approach.
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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.