ArticleThe Journal of biological chemistry2010
Tgfbeta signaling directly induces Arf promoter remodeling by a mechanism involving Smads 2/3 and p38 MAPK.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Identification of Paxillin as a Prognostic Factor for Glioblastoma via Integrated Bioinformatics Analysis.BioMed research international · 2022Pooled it
- A Bayesian-Based Integrative Bioinformatics Analysis Nominates Oncogenic Drivers in Neuroblastoma.Clinical and translational science · 2026Article
- Methyltransferase Inhibition Enables TgfMolecular and cellular biology · 2023Article
- Exon skipping in genes encoding lineage-defining myogenic transcription factors in rhabdomyosarcoma.Cold Spring Harbor molecular case studies · 2022Article
- Transcriptional regulation of INK4/ARF locus by cis and trans mechanisms.Frontiers in cell and developmental biology · 2022Review
- HaCaT‑conditioned medium supplemented with the small molecule inhibitors SB431542 and CHIR99021 and the growth factor PDGF‑AA prevents the dedifferentiation of dermal papilla cellsMolecular medicine reports · 2021Article
- Post-Translational Regulation of ARF: Perspective in Cancer.Biomolecules · 2020Review
- Bayesian Modeling Identifies PLAG1 as a Key Regulator of Proliferation and Survival in Rhabdomyosarcoma Cells.Molecular cancer research : MCR · 2020Article
- Testis-specific Arf promoter expression in a transposase-aided BAC transgenic mouse model.Molecular biology reports · 2019Article
- Identification ofMolecular cancer research : MCR · 2019Article
- Regulatory Network of ARF in Cancer Development.Molecules and cells · 2018Review
- Dynamics of ARF regulation that control senescence and cancer.BMB reports · 2016Review
- Acute Effects of Transforming Growth Factor-β1 on Neuronal Excitability and Involvement in the Pain of Rats with Chronic Pancreatitis.Journal of neurogastroenterology and motility · 2016Article
- p19(Arf) limits primary vitreous cell proliferation driven by PDGF-B.Experimental eye research · 2016Article
- The epigenetic modifier JMJD6 is amplified in mammary tumors and cooperates with c-Myc to enhance cellular transformation, tumor progression, and metastasis.Clinical epigenetics · 2016Article
- Upregulation of cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on magnesium alloy surface coating with tricalcium phosphate.Journal of materials science. Materials in medicine · 2015Article
- Isolation and characterization of mammalian cells expressing the Arf promoter during eye development.BioTechniques · 2014Article
- miR-27 negatively regulates pluripotency-associated genes in human embryonal carcinoma cells.PloS one · 2014Article
- Varied manifestations of persistent hyperplastic primary vitreous with graded somatic mosaic deletion of a single gene.Molecular vision · 2014Article
- A distant, cis-acting enhancer drives induction of Arf by Tgfβ in the developing eye.Developmental biology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
We have investigated how the Arf gene product, p19(Arf), is activated by Tgfβ during mouse embryo development to better understand how this important tumor suppressor is controlled. Taking advantage of new mouse models, we provide genetic evidence that Arf lies downstream of Tgfβ signaling in cells arising from the Wnt1-expressing neural crest and that the anti-proliferative effects of Tgfβ depend on Arf in vivo. Tgfβ1, -2, and -3 (but not BMP-2, another member of the Tgfβ superfamily) induce p19(Arf) expression in wild type mouse embryo fibroblasts (MEFs), and they enhance Arf promoter activity in Arf(lacZ/lacZ) MEFs. Application of chemical inhibitors of Smad-dependent and -independent pathways show that SB431542, a Tgfβ type I receptor (TβrI) inhibitor, and SB203580, a p38 MAPK inhibitor, impede Tgfβ2 induction of Arf. Genetic studies confirm the findings; transient knockdown of Smad2, Smad3, or p38 MAPK blunt Tgfβ2 effects, as does Cre recombinase treatment of Tgfbr2(fl/fl) MEFs to delete Tgfβ receptor II. Chromatin immunoprecipitation reveals that Tgfβ rapidly induces Smads 2/3 binding and histone H3 acetylation at genomic DNA proximal to Arf exon 1β. This is followed by increased RNA polymerase II binding and progressively increased Arf primary and mature transcripts from 24 through 72 h, indicating that increased transcription contributes to p19(Arf) increase. Last, Arf induction by oncogenic Ras depends on p38 MAPK but is independent of TβrI activation of Smad 2. These findings add to our understanding of how developmental and tumorigenic signals control Arf expression in vivo and in cultured MEFs.
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Registered trials
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