ArticleProceedings of the National Academy of Sciences of the United States of America2011
Egr1 mediates p53-independent c-Myc-induced apoptosis via a noncanonical ARF-dependent transcriptional mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 128 citations in OpenAlex.
- Trial
- Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Chitosan/β-cyclodextrin nanocarriers enhance 5-fluorouracil efficacy against colorectal cancer via pH-responsive release and apoptosis modulation.Scientific reports · 2026Article
- Role of NPPB for recovery post ventricular assist device in paediatric dilated cardiomyopathy: Single-cell multiomics.ESC heart failure · 2025Article
- The Nucleolus: A Central Hub for Ribosome Biogenesis and Cellular Regulatory Signals.International journal of molecular sciences · 2025Review
- Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention.Journal of cell science · 2024Article
- Synergy between BRD9- and IKZF3-Targeting as a Therapeutic Strategy for Multiple Myeloma.Cancers · 2024Article
- The relationship between keratin 18 and epithelial-derived tumors: as a diagnostic marker, prognostic marker, and its role in tumorigenesis.Frontiers in oncology · 2024Review
- EGR1/Cancer biology & therapy · 2023Article
- Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension.Human molecular genetics · 2023Article
- Article
- Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability.Nature communications · 2023Article
- EGR1 Haploinsufficiency Confers a Fitness Advantage to Hematopoietic Stem Cells Following Chemotherapy.Experimental hematology · 2022Article
- Early Growth Response 1 Strengthens Pol-III-Directed Transcription and Transformed Cell Proliferation by Controlling PTEN/AKT Signalling Activity.International journal of molecular sciences · 2022Article
- Characterization of Novel α-Mangostin and Paeonol Derivatives With Cancer-Selective Cytotoxicity.Molecular cancer therapeutics · 2022Article
- MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding.Cancer research communications · 2022Article
- Article
- RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation.BMC genomic data · 2021Article
- Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines.International journal of molecular sciences · 2021Article
- Deuterium Oxide (DCancers · 2021Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
c-Myc is frequently deregulated in human cancers. Although deregulated c-Myc leads to tumor growth, it also triggers apoptosis in partnership with tumor suppressors such as ARF and p53. Apoptosis induced by c-Myc is a critical fail-safe mechanism for the cell to protect against unrestrained proliferation. Despite the plethora of information on c-Myc, the molecular mechanism of how c-Myc induces both transformation and apoptosis is unclear. Oncogenic c-Myc can indirectly induce the expression of the tumor suppressor ARF, which leads to apoptosis through the stabilization of p53, but both c-Myc and ARF have apoptotic activities that are independent of p53. In cells without p53, ARF directly binds to c-Myc protein and inhibits c-Myc-induced hyperproliferation and transformation with a concomitant inhibition of canonical c-Myc target gene induction. However, ARF is an essential cofactor for p53-independent c-Myc-induced apoptosis. Here we show that ARF is necessary for c-Myc to drive transcription of a unique noncanonical target gene, Egr1. In contrast, c-Myc induces another family member, Egr2, through a canonical mechanism that is inhibited by ARF. We further demonstrate that Egr1 is essential for p53-independent c-Myc-induced apoptosis, but not ARF-independent c-Myc-induced apoptosis. Therefore, ARF binding switches the inherent activity of c-Myc from a proliferative to apoptotic protein without p53 through a unique noncanonical transcriptional mechanism. These findings also provide evidence that cofactors can differentially regulate specific transcriptional programs of c-Myc leading to different biological outcomes.
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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.