ArticleScientific reports2016
TGF-β induces p53/Smads complex formation in the PAI-1 promoter to activate transcription.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 80 citations in OpenAlex.
- SERPINE1 (PAI-1) Regulation in Mechanotransduction-Associated Cellular Senescence.Journal of cellular biochemistry · 2026Review
- The miR-16-1-3p suppresses proliferation and invasiveness via the MDM2-p53 axis in TGF-β1 signaling in osteosarcoma.Molecular therapy. Oncology · 2026Article
- Differential regulation of immunoglobulin class switch recombination by the tumor suppressor p53.Scientific reports · 2026Article
- TGF-β/SMAD signaling maintains nucleus pulposus stem cell quiescence to protect against oxidative injury in intervertebral disc degeneration.Stem cell research & therapy · 2026Article
- LCRMP-1 induces tumor angiogenesis by transcriptionally upregulating SERPINE1 in lung adenocarcinoma.Communications biology · 2025Article
- Insights into the Cellular and Molecular Mechanisms behind the Antifibrotic Effects of Nerandomilast.American journal of respiratory cell and molecular biology · 2025Article
- Modeling oxaliplatin resistance in colorectal cancer reveals a SERPINE1-based gene signature (RESIST-M) and therapeutic strategies for pro-metastatic CMS4 subtype.Cell death & disease · 2025Article
- The Molecular Interplay Between p53-Mediated Ferroptosis and Non-Coding RNAs in Cancer.International journal of molecular sciences · 2025Review
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- Structural and mechanistic diversity in p53-mediated regulation of organismal longevity across taxonomical orders.PLoS computational biology · 2025Article
- A Novel Mechanism of the p53 Isoform Δ40p53α in Regulating Collagen III Expression in TGFβ1-Induced LX-2 Human Hepatic Stellate Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Analysis of Stratifin Expression and Proteome Variation in a Rat Model of Acute Lung Injury.Journal of proteome research · 2025Article
- Endothelial senescence induced by PAI-1 promotes endometrial fibrosis.Cell death discovery · 2025Article
- TGF-β induces cholesterol accumulation to regulate the secretion of tumor-derived extracellular vesicles.Journal of experimental & clinical cancer research : CR · 2025Article
- Cellular Senescence in Endometrium: A Pivotal Regulator in Physiological Remodeling and Pathological Disorders.International journal of biological sciences · 2025Review
- CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling.Cell death & disease · 2024Article
- Advances in Traditional Chinese Medicine research in diabetic kidney disease treatment.Pharmaceutical biology · 2024Review
- FRMD6 determines the cell fate towards senescence: involvement of the Hippo-YAP-CCN3 axis.Cell death and differentiation · 2024Article
- Sarcomatoid carcinoma of the pancreas (Review).Oncology letters · 2024Review
- Analysis of the DNA-binding properties of TGF-β-activated Smad complexes unveils a possible molecular basis for cellular context-dependent signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor β (TGF-β) signaling facilitates tumor development during the advanced stages of tumorigenesis, but induces cell-cycle arrest for tumor suppression during the early stages. However, the mechanism of functional switching of TGF-β is still unknown, and it is unclear whether inhibition of TGF-β signaling results amelioration or exacerbation of cancers. Here we show that the tumor suppressor p53 cooperates with Smad proteins, which are TGF-β signal transducers, to selectively activate plasminogen activator inhibitor type-1 (PAI-1) transcription. p53 forms a complex with Smad2/3 in the PAI-1 promoter to recruit histone acetyltransferase CREB-binding protein (CBP) and enhance histone H3 acetylation, resulting in transcriptional activation of the PAI-1 gene. Importantly, p53 is required for TGF-β-induced cytostasis and PAI-1 is involved in the cytostatic activity of TGF-β in several cell lines. Our results suggest that p53 enhances TGF-β-induced cytostatic effects by activating PAI-1 transcription, and the functional switching of TGF-β is partially caused by p53 mutation or p53 inactivation during cancer progression. It is expected that these findings will contribute to optimization of TGF-β-targeting therapies for cancer.
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