ArticleThe Journal of biological chemistry2013
The cyclin-dependent kinase inhibitor p16INK4a physically interacts with transcription factor Sp1 and cyclin-dependent kinase 4 to transactivate microRNA-141 and microRNA-146b-5p spontaneously and in response to ultraviolet light-induced DNA damage.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Obesity-related Metabolic Dysfunction and Triple-negative Breast Cancer: Epidemiologic Signals, Mechanistic Pathways, and Opportunities for Prevention.Current obesity reports · 2026Review
- Senescent-Like Myofibers Contribute to Anti-Regenerative Cytokine Signaling in Duchenne Muscular Dystrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A narrative review of therapy-induced senescence in cancer: mechanisms, immune interplay, and therapeutic opportunities.Journal of the Egyptian National Cancer Institute · 2025Review
- p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice.Neuron · 2025Article
- The interplay of p16INK4a and non-coding RNAs: bridging cellular senescence, aging, and cancer.Biogerontology · 2025Review
- The interplay of p16INK4a and non-coding RNAs: bridging cellular senescence, aging, and cancer.Biogerontology · 2025Review
- P16INK4A-More Than a Senescence Marker.Life (Basel, Switzerland) · 2022Review
- Article
- p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade.Cancer research · 2022Article
- Review
- Dose and time effects of solar-simulated ultraviolet radiation on the in vivo human skin transcriptome.The British journal of dermatology · 2020Article
- Interleukin-8 Dedifferentiates Primary Human Luminal Cells to Multipotent Stem Cells.Molecular and cellular biology · 2020Article
- p16INK4a inhibits the proliferation of osteosarcoma cells through regulating the miR-146b-5p/TRAF6 pathway.Bioscience reports · 2019Article
- p16: cycling off the beaten path.Molecular & cellular oncology · 2019Article
- Obesity and p16Molecular and cellular biology · 2017Article
- p16Molecular carcinogenesis · 2017Article
- Senescence-Associated MicroRNAs.International review of cell and molecular biology · 2017Review
- Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel.International journal of molecular sciences · 2016Article
- Role of microRNAs Located on Chromosome Arm 10q in Malignant Gliomas.Brain pathology (Zurich, Switzerland) · 2016Article
- MiR-141 Inhibits Gastric Cancer Proliferation by Interacting with Long Noncoding RNA MEG3 and Down-Regulating E2F3 Expression.Digestive diseases and sciences · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
p16(INK4a) is a tumor suppressor protein involved in several stress-related cellular responses, including apoptosis. Recent lines of evidence indicate that p16(INK4a) is also a modulator of gene expression. However, the molecular mechanisms underlying this novel function are still obscure. Here, we present clear evidence that p16(INK4a) modulates the levels of various microRNAs, with marked positive effect on miR-141 and miR-146b-5p. This effect is mediated through the formation of the p16-CDK4-Sp1 heterocomplex, which binds to Sp1 consensus-binding motifs present in the promoters of miR-141 and miR-146b-5p, and it enables their transcription. In addition, we have shown that p16(INK4a) interacts with Sp1 through the fourth ankyrin repeat, which is crucial for Sp1 binding to the miR-141 and miR-146b-5p promoters and their transcriptional activation. The physiological importance of this association was revealed by the inability of cancer-related p16(INK4a) mutants to interact with Sp1. Moreover, we have shown p16-CDK4-Sp1-dependent up-regulation of miR-141 and miR-146b-5p following UV light-induced DNA damage and the role of these two microRNAs in mediating p16-related induction of apoptosis in response to this genotoxic stress. Together, these results indicate that p16(INK4a) associates with CDK4 not only to inhibit the cell cycle but also to enable the transcription of two important onco-microRNAs, which act as downstream effectors.
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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.